Ameliorative effect of Ganoderma lucidum on carbon tetrachloride-induced liver fibrosis in rats

AIM: To investigate the effects of Reishi mushroom, Ganoderma lucidum extract (GLE), on liver fibrosis induced by carbon tetrachloride (CO) in rats. METHODS: Rat hepatic fibrosis was induced by CCl4. Forty Wistar rats were divided randomly into 4 groups: control, CCl4, and two GLE groups. Except for rats in control group, all rats were administered orally with CCl4 (20%, 0.2 mL/100 g body weight) twice a week for 8 weeks. Rats in GLE groups were treated daily with GLE (1 600 or 600 mg/kg) via gastrogavage throughout the whole experimental period. Liver function parameters, such as ALT, AST, albumin, and albumin/globulin (A/G) ratio, spleen weight and hepatic amounts of protein, malondiladehyde (MDA) and hydroxyproline (HP) were determined. Histochemical staining of Sirius red was performed. Expression of transforming growth factorβ1 (TGF-β1), methionine adenosyltransferase (MAT1) 1A and MAT2A mRNA were detected by using RT-PCR. RESULTS: CCU caused liver fibrosis, featuring increase in plasma transaminases, hepatic MDA and HP contents, and spleen weight; and decrease in plasma albumin, A/G ratio and hepatic protein level. Compared with CCU group, GLE (600, 1 600 mg/kg) treatment significantly increased plasma albumin level and A/G ratio (P<0.05) and reduced the hepatic HP content (P<0.01). GLE (1 600 mg/kg) treatment markedly decreased the activities of transaminases (P<0.05), spleen weight (P<0.05) and hepatic MDA content (P<0.05); but increased hepatic protein level (P<0.05). Liver histology in the GLE (1 600 mg/kg)-treated rats was also improved (P<0.01). RT-PCR analysis showed that GLE treatment decreased the expression of TGF-β1(P<0.05-0.001) and changed the expression of MAT1A (P<0.05-0.01) and MAT2A (P<0.05-0.001). CONCLUSION: Oral administration of GLE significantly reduces CCl4-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular necrosis by its free-radical scavenging ability.     

Effects of PPARg agonist pioglitazone on rat hepatic fibrosis

AIM: To investigate effects of pioglitazone on rat hepatic fibrosis and to explore its mechanism. METHODS: Rat hepatic fibrosis was induced by carbontet. achloride (CCI4). Forty Sprague-Dawley rats were divided randomly into 4 groups: control, model, and two treatment (PⅠ, PⅡ) groups. Except for rats in control group, all rats were given subcutaneous injection of 400 mL/L CCI4, twice a wk for 8 wk. Rats in PⅠ and PⅡ groups were also treated with pioglitazone of 3 mg/kg, daily via gastrogavage beginning on the 1^st day and at the end of the 2^nd week, administration of CCI4 respectively. Liver functions (ALT, AST), serum fibrotic markers (HA, LN, PCIII) and hepatic hydroxyproline (HP) concentration were determined respectively. Histochemical staining of formalin-fixed liver sections with HE, Masson-Trichrome, and immunohistochemical staining for m-smooth muscle actin (α-SMA) were performed. Modified Knodell and Chevallier semi-quantitative scoring system (SSS) was used to evaluate necroinflammatory activity and fibrosis degree. RESULTS: Compared with model group, pioglitazone significantly reduced the serum levels of ALT, AST, HA, LN and PCⅢ (P&lt;0.05 or &lt;0.01). The HP concentrations in PⅠ(210.90&#177;24.07 μg/g), and PⅡ (257.36&#177;30.55 μg/g) groups were also lower than those in model group (317.80&#177;36.44) μg/g) (P&lt;0.01). Histologic examination showed that PⅠ and PⅡ groups had milder hepatocellular degeneration, necrosis and infiltration of inflammatory cells, and thinner or less fibrotic septa than did model group. The scores for necroinflammation in P (2.80&#177;1.03), and PⅡ (3.00&#177;1.05) groups were significantly reduced as compared with model group (4.88&#177;2.30) (P&lt;0.05 or &lt;0.01); the fibrosis scores in PⅠ (3.40&#177;1.65), and PⅡ (4.60&#177;1.35) groups were also markedly lower than those in model group (7.00&#177;3.21) (P&lt;0.05 or &lt;0.01). Immunohistochemical staining showed that expression of α-SMA in PⅠ and PⅡ groups was ameliorated dramatically compared with model group. CONCLUSION: PPARγ, agonist pioglitazone greatly retards the progression of rat hepatic fibrosis induced by CCI4 through inhibition of HSC activation and amelioration of hepatocyte necroinflammation in rats.     

Effects of extract from Ginkgo biloba on carbon tetrachloride-induced liver injury in rats

AIM: To study the effects of extract from Ginkgo biloba (EGb) containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride (CCl4). METHODS: All rats were randomly divided into control group, CCl4-treated group, colchicine-treated group and EGb-protected group. Chronic liver injury was induced in experimental groups by subcutaneous injection of CCl4 and fed with chows premixed with 79.5% corn powder, 20% lard and 0.5% cholesterol (v/v). EGb-protected group was treated with EGb (0.5 g/kg body weight per day) for 7 wk. At the end of wk 8, all the rats were killed. Liver function, liver fibrosis, oxidative stress and expression of transforming growth factorβ1 (TGF-β1), a-smooth muscle actin (α-SMA) and typeⅠcollagens in liver were determined. In addition, pathology changes of liver tissue were observed under light microscope. RESULTS: The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin (Alb) in EGb-protected group were notably improved as compared with the CCL4-treated group (P < 0.01). The contents of serum hyaluronic acid (HA), typeⅢprocollagen (PCⅢ), typeⅣcollagen (CIV) and the expression of hepatic tissue TGF-β1,α-SMA and typeⅠcollagen in EGb-protected group were significantly lower than those in CCL4-treated groups (P < 0.05, P < 0.01). The degrees of liver fibrosis in EGb-protected groups were lower than those in CCL4-treated groups (6.58±1.25 vs 9.52±2.06, P < 0.05). Compared to the CCL4-treated group, the levels of plasma glutathoine peroxidase (Se-GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) were strikingly improved also in EGb-protected group (P < 0.05, P < 0.01). CONCLUSION: EGb resists oxidative stress and thereby reduces chronic liver injury and liver fibrosis in rats with liver injury induced by CCl4     

Effect of WeiJia on carbon tetrachloride induced chronic liver injury

AIM:To study the effect of WeiJia on chronic liver injuryusing carbon tetrachloride(CCl_4)induced liver injuryanimal model.METHODS:Wistar rats weighing 180-220g were ran-domly divided into three groups:normal control group(Group A),CCl_4 induced liver injury control group(GroupB)and CCl_4 induction with WeiJia treatment group(GroupC).Each group consisted of 14 rats.Liver damage andfibrosis was induced by subcutaneous injection with 40?l_4 in olive oil at 3 mL/kg body weight twice a week foreight weeks for Groups B and C rats whereas olive oilwas used for Group A rats.Starting from the third week,Group C rats also received daily intraperitoneal injectionof WeiJia at a dose of 1.25 μg/kg body weight.Animalswere sacrificed at the fifth week(4 male,3 female),andeighth week(4 male,3 female)respectively.Degree offibrosis were measured and serological markers for liverfibrosis and function including hyaluronic acid(HA),typeIV collagen(CIV),γ-glutamyl transferase(γ-GT),alanineaminotransferase(ALT)and aspartate aminotransferase(AST)were determined.Alpha smooth muscle actin (α-SMA)and proliferating cell nuclear antigen(PCNA)immunohistochemistry were also performed.RESULTS:CCl_4 induction led to the damage of liver anddevelopment of fibrosis in Group B and Group C ratswhen compared to Group A rats.The treatment of WeiJiain Group C rats could reduce the fibrosis condition sig-nificantly compared to Group B rats.The effect could beobserved after three weeks of treatment and was moreobvious after eight weeks of treatment.Serum HA,CIV,ALT,AST and γ-GT levels after eight weeks of treatmentfor Group C rats were 58±22 μg/L(P<0.01),57±21 μg/L(P<0.01),47±10 U/L(P<0.01),139±13 U/L(P<0.05)and 52±21 U/L(P>0.05)respectively,similar to normalcontrol group(Group A),but significantly different fromCCl_4 induced liver injury control group(Group B).An in-crease in PCNA and decrease in α-SMA expression levelwas also observed.CONCLUSION:WeiJia could improve liver function andreduce liver fibrosis which might be through the inhibi-tion of stellate cell activity.     

Study on hepatoprotective effect of peptide S-8300 from shark liver

AIM: To explore the effects of peptide S-8300 from shark liver (S-8300) on liver function as well as in regulating immune functions in experimental injury models. METHODS: Mice were administered with different doses of S-8300 for four consecutive days, followed by mice injected with tetrachloromethane (CCI4) on d 3. The activity of ALT, AST, LDH, SOD and contents of MDA and GSH in the mice liver were tested. And mice were treated with Cy (100 mg/kg) at the beginning of the experiment to induce immunosuppression model. The S-8300 groups were treated with S-8300 seven days after the beginning of Cy administration. The effects of S-8300 on the formulation of serum hemolysin and the content of IL-2 in serum in the immunosuppression mice were observed. RESULTS: S-8300 obviously decreased the level of ALT (52.2±11.0 U/dL vs135.9±6.5 U/dL, P<0.01), AST (67.5±6.9 U/dL vs 238.8±8.7 U/dL, P<0.01), LDH (155.1±46.8 U/dL vs 240.4±6.0 U/dL, P<0.01) & MDA (0.64?.027 nmol/mg vs 1.06±0.040 nmol/mg, P<0.01) and increased SOD (24.51±1.01 U/mg vs 19.05±0.73 U/mg, P<0.01) & GSH (24.17±0.91 μg/mg vs 14.93±0.45 μg/mg, P<0,01) in mice liver damaged by CCI4. S-8300 also markedly improved the formulation of serum hemolysin (0.094±0.005 A540 vs 0.063±0.006 A540, P<0.01) and increased the level of IL-2 (9.74±1.16 pg/mL vs 5.81±0.87 pg/mL, P<0.01) in serum of the immunosuppression mice. CONCLUSION: The results suggested S-8300 has significant hepatoprotective, immunomodulatory and inhibiting of lipid peroxidation activity.     

Gadolinium chloride and salvia miltiorrhiza compound ameliorate reperfusion injury in hepatocellular mitochondria

AIM: To investigate the effect of gadolinium chloride (GaCl3)and salvia miltiorrhiza compound (SMCo) on ischemia and reperfusion (I/R) injury in hepatocellular mitochondria.METHODS: Wistar rats were randomly to divided into control group, GaCl3 group, SMCo group and GaCl3 + SMCo group (n=15 each). GaCl3 (7 rmg@kg-1) was injected into tail vein on d 1 and d 2 in contrast group. SMCo ( 2 ml@kg-1) was injected into muscle on d 1 and d 2 in SMCo group. GaCl3+SMCo group received both GaCl3 (iv) and SMCo (im) injection. Control group received saline injection only. On d 3, all the rats were subjected to 2 h ischemia in the middle and left lobes of the liver, followed by reperfusion for 2 h, 6 h and 18 h respectively. The level of serum alanine aminotransferase (ALT) and malondialdehyde (MDA) in hepatocellular mitochondria was measured. Pathological changes in hepatic tissue and in hepatocellular mitochondria were determined with optical microscope and electronic microscope, respectively.RESULTS: Remarkablly pathohistological and biochemical changes were detected after 6 h of I/R. Compared with control, the level of ALT was decreased in GaCl3, SMCo and GaCl3+SMCo treated groups (1 314.0±278.7 vs809.4±196.1,716.6±242.8 and 837.2±190.6 IU@L-1, respectively. P＜0.05).Similarly, the level of MDA was decreased in GaCl3, SMCo and GaCl3+SMCo treated groups (293.1±±51.1 vs 190.8±55.5,214.3±32.9 and 221.0±47.3 nmol@g-1, respectively, P＜0.05).Accordingly, in control group, swelling, degeneration, focal necrosis, infilt-ation of leucocyte were found in reperfused tissue under an optical microscope, and mitochondda swelling, rupture and even breakdown were seen under an electronic microscope.These pathohistological and ultrastructural damages caused by I/R were greatly attenuated in GaCl3, SMCo and GaCl3+SMCo treated groups. However, there was no additive effect observed when GaCl3 and SMCo were used together.CONCLUSION: Both GaCl3 and SMCo can alleviate the I/Rinjury in hepatocellular mitochondria.     

Inhibitory effect of Huangqi Zhechong decoction on liver fibrosis in rat

AIM: To assess the inhibitory effect of Huangqi Zhechong decoction on hepatic fibrosis in rats induced by CCl(4) plus alcohol and high fat low protein diet. METHODS: Male SD rats were randomly divided into hepatic fibrosis model group, control group and 3 treatment groups consisting of 12 rats in each group. Except for the normal control group, all the rats were subcutaneously injected with CCl(4) at a dosage of 3 mL/kg. In 3 treated groups, either high-dose group (9 mL/kg), or medium-dose group (6 mL/kg), or low-dose group (3 mL/kg) was daily gavaged with Huangqi Zhechong decoction, and saline vehicle was given to model and normal control rats. Enzyme-linked immunosorbent assay (ELISA) and biochemical examinations were used to determine the changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN), type-III-procollagen-N-peptide (PIIIP), and type IV collagen content in serum, and hydroxyproline (Hyp) content in liver after sacrificing the rats. Pathologic changes, particularly fibrosis were examined by hematoxylin and eosin (HE) and Van Gieson staining. RESULTS: Compared with the model control group, serum ALT, AST, HA, LN, PIIIP and type IV collagen levels dropped markedly in Huangqi Zhechong decoction groups, especially in the medium-dose Huangqi Zhechong decoction group (1 954+/-576 U/L vs 759+/-380 U/L, 2 735+/-786 U/L vs 1 259+/-829 U/L, 42.74+/-7.04 ng/mL vs 20.68+/-5.85 ng/mL, 31.62+/-5.84 ng/mL vs 14.87+/-1.45 ng/mL, 3.26+/-0.69 ng/mL vs 1.47+/-0.46 ng/mL, 77.68+/-20.23 ng/mL vs 25.64+/-4.68 ng/mL, respectively) (P<0.05). The Hyp content in liver tissue was also markedly decreased (26.47+/-11.24 mg/mgprot vs 9.89+/-3.74 mg/mgprot) (P<0.01). Moreover, the stage of the rat liver fibrosis in Huangqi Zhechong decoction groups was lower than that in model group, and more dramatic drop was observed in medium-dose Huangqi Zhechong decoction group (P<0.01). CONCLUSION: Huangqi Zhechong decoction can inhibit hepatic fibrosis resulted from chronic liver injure, retard the development of cirrhosis, and notably ameliorate the liver function. It may be a safe and effective therapeutic drug for patients with fibrosis.     

Effect of Chinese medicine Qinggan Huoxuefang on inducing HSC apoptosis in alcoholic liver fibrosis rats

AIM: To investigate the effect of Qinggan Huoxuefang (QGHXF) on improvement of liver function and pathology in rats, and to analyze the mechanism. METHODS: Wistar rats were divided into three groups at random: normal control group (12), micro-amount carbon tetrachloride group (CCl4)(12) and model group A (60). The model group A was ingested with the mixture (500 mL/L alcohol, 8 mL/kg per day; corn oil, 2 mL/kg per day; pyrazole, 24 mg/kg per day) once a day and intraperitoneal injections of 0.25 mL/kg of a 250 mL/L solution of CCl4 in olive oil twice a week for 12 wk. The CCl4 group received intraperitoneal injections only. At the end of 8 wk the model group A (60) was divided into 5 subgroups: model group, Xiaochaihu Chongji (XCH) group, QGHXF high dose group, moderate dose group and low dose group, and were given the drugs respectively. At the end of 12 wk, all the rats were killed and blood samples collected, as well as liver tissue. Blood samples were used for evaluation of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (γ-GT). Liver specimens were obtained for routine HE, apoptosis gene array and flow cytometry analysis. RESULTS: A liver fibrosis animal model was successfully established. Fibrosis was obviously reduced in QGHXF high dose group, and no fibrosis formed in CCl4 group. Compared with model group the QGHXF group and XCH group could obviously decrease the level of ALT, AST, ALP, and GGT (P<0.05). QGHXF high dose group was better than XCH group in ALT (615±190 vs 867±115), and AST(1972±366 vs 2777±608). Moreover, QGHXF could reduce liver inflammation, fibrosis-induced hepatic stellate cell (HSC) apoptosis and regulate apoptosis gene expression. The HSC apoptosis rates of QGHXF groups were 22.4±3.13, 13.79±2.26 and 10.07±1.14, higher than model group, 6.58±1.04 (P< 0.05). Compared to model group, 39 genes were up-regulated, 11 solely expressed and 17 down-regulated in high dose group. CONCLUSION: QGHXF can improve liver fibrosis and induce HSC apoptosis.     

Effects of estradiol on liver estrogen receptor-alpha and its mRNA expression in hepatic fibrosis in rats

AIM:Estradiol treatment regulates estrogen receptor (ER) level in normal rat liver.However,little information is available concerning the role of estrogen in regulating liver ER in hepatic fibrosis in rats.The present study was conducted to determine whether estradiol treatment in CCl4-induced liver fibrosis of female and ovariectomized rats altered liver ERα and its mRNA expression,and to investigate the possible mechanisms.METHODS:Seventy female rats were divided into seven groups with ten rats in each. The ovariectomy groups were initiated with ovariectomies and the sham operation groups were initiated with just sham operations.The CCl4 toxic fibrosis groups received 400mL/L CCI4 subcutaneously at a dose of 2 mL/kg twice weekly.Estrogen groups were treated subcutaneously with estradiol 1mg/kg, the normal control group and an ovariectomy group received injection of peanut oil vehicle twice weekly.At the end of 8 weeks,all the rats were killed to detect their serum and hepatic indicators,their hepatic collagen content, and liver ER and ER mRNA expression.RESULTS: Estradiol treatment in both ovariectomy and sham ovariectomy groups reduced liver levels of ALT (from 658&#177;220nkat/L to 311&#177;146nkat/L and 540&#177;252nkat/L to 314&#177;163nkat/L,P&lt;0.05) and AST (from 697&#177;240nkat/L to 321&#177;121nkat/L and 631&#177;268nkat/L to 302&#177;153nkat/L,P&lt;0.05),increased serum nitric oxide (NO) level (from 53.7&#177;17.1μmol/L to 93.3&#177;4.2μmol/L and 55.3&#177;3.1μmol/Lto 87.5&#177;23.6μmol/L, P&lt;0.05) and hepatic nitric oxide synthase (NOS) activity (from 1.73&#177;0.71KU/g to 2.49&#177;1.20KU/g and 1.65&#177;0.46KU/g to 2.68&#177;1.17KU/g, P&lt;0.05),diminished the accumulation of hepatic collagen,decreased centrolobular necrotic areas as well as the inflammatory reaction in rats subjected to CCl4. The positive signal of ER and ER mRNA distributed in parenchymal and non-parenchymal hepatic cells,especially near the hepatic centrolobular and periportal areas.Ovariectomy decreased ER level (from 10.2&#177;3.2 to 4.3&#177;1.3) and ER mRNA expression (from 12.8&#177;2.1 to 10.9&#177;1.3) significantly (P&lt;0.05). Hepatic ER and ER mRNA concentrations were elevated after treatment with estradiol in both ovariectomy (15.8&#177;2.4, 20.8&#177;3.1) and sham ovariectomy(18.7&#177;3.8, 23.1&#177;3.7) fibrotic groups (P&lt;O.05).CONCLUSION: The increase in hepatic ER and mRNA expression may be part of the molecular mechanisms underlying the suppressive effect of estradiol on liver fibrosis induced by CCI4 administration.     

Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis

AIM To evaluate the antifibrotic effect ofdifferent doses of recombinant human Gamma-Interferon (IFN-γ) in two rat models of hepaticfibrosis, and to observe its effect on moderatechronic hepatitis B virus fibrosis.METHODS Hepatic fibrosis was successfullyinduced in 150 and 196 rats by subcutaneousinjection of carbon tetrachloride (CCl_4) andintraperitoneal injection of dimethylnitrosamine(DMN), respectively. Each of the two modelgroups was divided into: ① fibrotic modelgroup; ② colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); ③ high-dose IFN-γ group (15 MU/kg per day, i.m. for 8weeks); ④ medium-dose IFN-γ group (5 MU/kgdaily, i.m. for 8 weeks); and ⑤ low-dose IFN-γgroup (1.67 MU/kg daily, i.m. for 8 weeks).Another group of 10 rats without any treatmentwas used as normal controls. At the end of theexperiment, semi-quantitative histopathologicalscores of inflammation and fibrosis, liversmooth muscle actin (α-SMA) expression level,liver hydroxyl proline content and serumhyaluronic acid levels were compared. And 47medium chronic hepatitis B viral fibrosispatients were studied. They were given IFN-γtreatment, 100MU/day i,m. for the first threemonths and 100MU qod i.m. for the next sixmonths. Semi-quantitative pathological scoresof inflammation and fibrosis and serum hepaticfibrosis indices were compared within the 9months.RESULTS In animal experiment, thepathological fibrosis scores and liver hydroxylproline content were found to be significantly lower in rats treated with different doses of IFN-γ as compared with rats in fibrotic model groupinduced by either CCl_4 or DMN, in a dose-dependent manner. For CCl_4-induced model,pathological fibrosis scores in high, medium andlow doses IFN-γ groups were 5. 10±2.88, 7.70±3.53 and 8.00±3.30, respectively, but the scorewas 14.60±7.82 in fibrotic model group.Hydroxyl proline contents were 2.83±1.18, 3.59±1.22 and 4.80±1.62, in the three IFN-γgroups, and 10.01±3.23 in fibrotic model group.The difference was statistically significant(P<0.01). Similar results were found in DMN-induced model. Pathological fibrosis scoreswere 6.30±0.48, 8.10±2.72 and 8.30±2.58, inhigh, medium and low doses IFN-γ groups, and12.60±3.57 in fibrotic model group. Hydroxylproline contents were 2.72±0.58, 3.14±0.71and 3.62±1.02, in the three IFN-γ groups, and12.79±1.54 in fibrotic model group. Thedifference was statistically significant(P<0.01). Serum hepatic fibrosis indicesdecreased significantly in the 47 patients afterIFN-γ treatment (HA: 433.38±373.00 vs 281.57±220.48; LN: 161.22±41.02 vs 146.35±44.67;PCⅢ: 192.59±89.95 vs 156.98±49.22; C-Ⅳ:156.30±44.01 vs 139.14±34.47) and thedifferences between the four indices weresignificant (P<0.05). Thirty-three patientsreceived two liver biopsies, one before and oneafter IFN-γ treatment. In thirty of 33 patientsIFN-γ had better effects according to semi-quantitative pathological scores (8.40±5.83 vs5.30±4.05, P<0.05).CONCLUSION All the three doses of IFN-γ areeffective in treating rat liver fibrosis induced byeither CCl_4 or DMN, the higher the dose, thebetter the effect. And IFN-γ is effective forpatients with moderate chronic hepatitis B viralfibrosis.     

Effect of enterokinetic prucalopride on intestinal motility in fast rats

AIM: To evaluate the effects of prucalopride on intestinal prokinetic activity in fast rats and to provide experimental basis for clinical treatrnent of gastrointestinal motility diseases.METHODS: Gastrointestinal propulsion rate was measured by the migration rate of activated charcoal, which reflexes gastrointestinal motility function. 120 Spraque-Dawley rats were randomly divided into four groups and received an intravenous injection of physiological saline (served as control), prucalopdde 1 mg/kg, prucalopride 2 mg/kg and cisapride 1 mg/kg,respectively. The gastrointestinal propulsion rate was measured 1, 2 or 4 hours after intravenous injection of the drugs.RESULTS: Significant accelerations of gastrointestinal propulsion rate in prucalopride 1 mg/kg and 2 mg/kg groups were found compared with control group at 2 and 4 hours (83.2%±5.5%, 81.7%±8.5% vs70.5%±9.2%, P＜0.01;91.2%±2.2%, 91.3%±3.9% vs86.8%±2.6%, P＜0.01).The gastrointestinal propulsion rates at 1, 2 or 4 hours were faster in prucalopride 1 mg/kg and 2 mg/kg groups than in cisapride group (84.0%±11.7%, 77.1%±11.9% vs 66.3%±13.6%, P＜0.01, P＜0.05; 83.2%±5.5%, 81.7%±8.5% vs75.4%±5.9 %, P＜0.01, P＜0.05; 91.2%±2.2%,91.3%±3.9% vs 88.6%±3.5%,P＜0.05, P＜0.05). No difference of gastrointestinal propulsion rate was found between prucalopride 1 mg/kg group and prucalopride 2 mg/kg group (P＞0.05).CONCLUSION: Prucalopride accelerates intestinal motility in fast rats, and has no dose dependent effect.     

Inhibitory effects of saikosaponin-d on CCl4-induced hepatic fibrogenesis in rats

AIM： To investigate the suppressive effect of saikosaponin-d （SSd） on hepatic fibrosis in rats induced by CCh injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-κB （NF-κB）, tumor necrosis factor-alpha （TNF-α） and interleukins-6 （IL-6）. METHODS： Hepatic fibrosis models were induced by subcutaneous injection of CCh at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses （1.0, 1.5 and 2.0 mg/kg） once daily for 6 wk in combination with CCh, while the control group received olive oil instead of CCh. At the end of the experiment, rats were anesthetized and killed （except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in lowdose group）. Hernatoxylin and eosin （HE） staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase （ALT）, triglyeride （TG）, albumin （ALB）, globulin （GLB）, hyaluronic acid （HA） and larninin （LN） in serum and the content of hydroxyproline （HYP） in liver were measured by biochemical examinations and radioimmuneoassay, respectively. In addition, the expression of TNF-α and IL-6 in liver homogenate was evaluated by enzymelinked immunosorbent assay （ELISA） and the levels of NF-κBp65 and I-κBa in liver tissue were analyzed by Western blotting. RESULTS： Both histological examination and Van Gieson staining demonstrated that SSd could attenuate the area and extent of necrosis and reduce the scores of liver fibrosis. Similarly, the levels of ALT, TG, GLB, HA, and LN in serum, and the contents of HYP, TNF-α and IL-6 in liver were all significantly increased in model group in comparison with those in control group. Whereas, the treatment with SScl markedly reduced all the above parameters compared with the model group, especially in the medium gr     

Role of L-carnitine in the prevention of acute liver damage induced by carbon tetrachloride in rats

BACKGROUND AND AIM: Lipid peroxidation is the most important mechanism in the pathogenesis of acute liver damage with carbon tetrachloride (CCl4). L-carnitine may prevent lipid peroxidation and thus may protect against liver damage. In the present study we investigated the protective effect of L-carnitine in experimental acute liver damage induced by CCl4. METHODS: Fifty rats were allocated to five equal groups. The first group was the control (group 1), the second group received an intraperitoneal CCl4 injection for 3 days (group 2), and the third group received a 50 mg/kg subcutaneous L-carnitine injection for 4 days, beginning a day before CCl4 injection. The CCl4 injection was continued for 3 days in the concerned group (group 3). Group 4 was given a CCl4 injection for 7 days and group 5 received a 50 mg/kg subcutaneous L-carnitine injection for 8 days, beginning a day before CCl4 injection. This group continued to receive a CCl4 injection for 7 days. Rats in groups 2 and 3 were killed on the fifth day. Rats in groups 1, 4 and 5 were killed on the ninth day. Plasma and liver tissue malondialdehyde (MDA) levels, glutathione peroxidase (GSH-Px) activity and liver enzyme levels were studied. Histopathological investigations were conducted. RESULTS: Liver tissue MDA levels decreased significantly in group 3 compared to group 2 (P<0.001). Liver tissue MDA levels in group 5 decreased significantly in comparison to those of group 4 (P<0.001). Liver tissue GSH-Px activity in group 5 was significantly lower than that in group 4 (P<0.05). There were no significant differences between groups 3 and 4 regarding GSH-Px activity (P>0.05). Steatosis, inflammation and necrosis in group 3 were significantly reduced when compared to group 2 (P<0.01). Fibrosis development was not identified in groups 2 and 3. Steatosis in group 5 was significantly lower than that in group 4 (P<0.05) and there were no significant differences between groups 4 and 5 with regards to inflammation and necrosis (P>0.05). Mild fibrosis development was identified in groups 4 and 5 but the difference between the groups was not significant. CONCLUSION: It appears that L-carnitine has a protective effect in the early stage of experimental acute liver damage induced by CCl4. As the toxic effect or damage continues, its effect lessens.     

Effect of Oxymatrine on the TGFbeta-Smad signaling pathway in rats with CCl4-induced hepatic fibrosis

AIM： To explore the anti-fibrotic effect of Oxymatrine on CCl4-induced liver fibrosis in rats and its modulation on the TGFbeta-Smad signaling pathway. METHODS： One hundred healthy male SD rats were randomly divided into three groups： normal group （n = 20）, treatment group of Oxymatrine （n = 40） and CCh-induced fibrosis group （n = 40）. Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride （CCh soluted in liquid paraffin with the concentration of 300 g/L, the dosage of injection was 3 mL/kg, twice per week for 8 wk）. The treated rats received Oxymatrine via celiac injection at a dosage of 10 mg/kg twice a week at the same time. The deposition of collagen was observed with H＆E and Masson staining. The concentration of serum TGF-β1 was assayed with ELISA. The gene expression of Smads and CBP （CREB binding protein） was detected with in situ hybridization （ISH） and immunohistochemistry （IH）, respectively. All the experimental figures were scanned and analyzed with special figure-analysis software. RESULTS： A significant reduction of collagen deposition and rearrangement of the parenchyma was noted in the liver tissue of Oxymatrine-treated rats. The semi- quantitative histological scores （2.43 ± 0.47 μm^2 vs 3.76 ±0.68, P 〈 0.05） and average area of collagen/in those rats were significantly decreased when compared with hepatic cirrhosis model rats （94.41 ± 37.26 μm^2 vs 290.86 ± 89.37 μm^2, P 〈 0.05）. The gene expression of Smad 3 mRNA was considerably decreased in the treated animals. The A value of Smad 3 mRNA was lower in the treated rats than the model rats （0.034 ± 0.090 vs 0.167 ± 0.092, P 〈 0.05）. Contrarily, the A value of Smad 7 mRNA was increased considerably in the treated animals （0.175 ± 0.065 vs 0.074 vs 0.012, P 〈 0.05）. There was an obvious decrease in the expression of CBP mRNA in treated rats as illuminated by a reduction of its A value when compared with model rats （0.065±0.049 vs 0.235 ?     

Protective effect of Weikang decoction and partial ingredients on model rat with gastric mucosa ulcer

AIM, To investigate the protective mechanisms of Weikang (WK) decoction on gastric mucosae. METHODS: Ninety rats were randomly divided into nine groups of 10 each, namely group, model group, group with large WK dosage, group with medium WK dosage, group with small WK dosage, group with herbs of jianpiyiqi (strengthening the spleen and replenishing qi), group with herbs of yangxuehuoxue (invigorating the circulation of and nourishing the blood), group with herbs of qingrejiedu (clearing away the heat-evils and toxic materials), group with colloidal bismuth pectin (CBP) capsules. According to the method adopted by Yang Xuesong, except normal control group, chronic gastric ulcer was induced with 100% acetic acid. On the sixth day after moldmaking, WK decoction was administered, respectively at doses of 20, 10 and 5 g/kg to rats of the WK groups, or the group swith herbs of jianpiyiqi, yangxuehuoxue and qingrejiedu, 10 mL/kg was separately administered to each group every day. For the group with CBP capsules, medicine was dissolved with water and doses 15 times of human therapeutic dose were administered (10 mL/kg solution containing 0.35% CBP). Rats of other groups were fed with physiological saline (10 mL/kg every day) .Administration lasted for 16 d. Rats were killed on d 22 after mold making to observe changes of gastric mucosa. The mucus thickness of gastric mucosa surface was measured. Levels of epidermal growth factor (EGF) in gastric juice, nitric oxide (NO) in gastric tissue, endothelin (ET) in plasma, superoxide dismutase (SOD) in plasma, malondialdehyde (MDA) in plasma and prostaglandin I2 (PGI2) were examined. RESULTS: Compared with control group, ulceration was found in gastric mucosa of model group rats. The mucus thickness of gastric mucosa surface, the levels of EGF, NO, 6-K-PGF1α and SOD decreased significantly in the model group (EGF: 0.818&#177;0.18 vs 2.168&#177;0.375, NO: 0.213&#177;0.049 vs0.601&#177;0.081, 6-K-PGF1α: 59.7&#177;6.3 vs 96.6&#177;8.30, SOD: 128.6&#177;15.0 vs 196.6&#177;35.3, P&lt;0.01), the levels of ET (179.96&#177;37.40 vs 46.64&#177;21.20, P&lt;0.01) and MDA (48.2&#177;4.5 vs 15.7&#177;4.8, P&lt;0.01) increased. Compared with model group, the thickness of regenerative mucosa increased, glandular arrangement was in order, and cystic dilative glands decreased, while the mucus thickness of gastric mucosa surface increased (20 g/kg WK: 51.3&#177;2.9 vs 23.2&#177;8.4, 10 g/kg WK: 43.3&#177;2.9 vs 23.2&#177;8.4, 5 g/kg WK：36.1&#177;7.2 vs 23.2&#177;8.4, jianpiyiqi: 35.4&#177;5.6 vs 23.2&#177;8.4, yangxuehuoxue: 33.1&#177;8.9 vs 23.2&#177;8.4, qingrejiedu: 31.0&#177;8.0 vs 23.2&#177;8.4 and CBP: 38.2&#177;3.5 vs 23.2&#177;8.4, P&lt;0.05-0.01). The levels of EGF (20 g/kg WK: 1.364&#177;0.12 vs 0.818&#177;0.18, 10 g/kg WK: 1.359&#177;0.24 vs 0.818&#177;0.18, 5 g/kg WK: 1.245&#177;0.31 vs 0.818&#177;0.18, jianpiyiqi： 1.025&#177;0.45 vs 0.818&#177;0.18, yangxuehuoxue: 1.03&#177;0.29 vs 0.818&#177;0.18, qingrejiedu: 1.02&#177;0.47 vs 0.818&#177;0.18 and CBP:1.237&#177;0.20 vs 0.818&#177;0.18, P&lt;0.05-0.01), NO (20 g/kg WK: 0.480&#177;0.026 vs 0.213&#177;0.049, 10 g/kg WK: 0.390&#177;0.055 vs 0.213&#177;0.049, 5 g/kg WK: 0.394&#177;0.026 vs 0.213&#177;0.049, jianpiyiqi: 0.393&#177;0.123 vs 0.213&#177;0.049, yangxuehuoxue: 0.463&#177;0.077 vs 0.213&#177;0.049, qingrejiedu: 0.382&#177;0.082 vs 0.213&#177;0.049 and CBP： 0.395&#177;0.053 vs 0.213&#177;0.049, P&lt;0.05-0.01), 6-K-PGF1α (20 g/kg WK: 86.8&#177;7.6 vs 59.7&#177;6.3, 10 g/kg WK: 77.9&#177;7.0 vs 59.7&#177;6.3, 5 g/kg WK:70.0&#177;5.4 vs 59.7&#177;6.3, jianpiyiqi: 73.5&#177;12.2 vs 59.7&#177;6.3, yangxuehuoxue: 65.1&#177;5.3 vs 59.7&#177;6.3, qingrejiedu: 76.9&#177;14.6 vs 59.7&#177;6.3, and CBP: 93.7&#177;10.7 vs 59.7&#177;6.3, P&lt;0.05-0.01) and SOD (20 g/kg WK: 186.4&#177;19.9 vs 128.6&#177;15.0, 10 g/kg WK: 168.2&#177;21.7 vs 128.6+15.0, 5 g/kg WK: 155.6&#177;21.6 vs 128.6&#177;15.0, jianpiyiqi: 168.0&#177;85.3 vs 128.6&#177;15.0, yangxuehuoxue: 165.0&#177;34.0 vs 128.6&#177;15.0, qingrejiedu: 168.2&#177;24.9 vs 128.6&#177;15.0, and CBP: 156.3&#177;18.1 vs 128.6&#177;15.0, P&lt;0.05-0.01) significantly increased. The levels of ET (20 g/kg WK: 81.30&#177;17.20 vs 179.96&#177;37.40, 10 g/kg WK: 83.40&#177;25.90 vs 179.96&#177;37.40, 5 g/kg WK: 93.87&#177;20.70 vs 179.96&#177;37.40, jianpiyiqi: 130.67&#177;43.66 vs 179.96&#177;37.40, yangxuehuoxue: 115.88&#177;34.09 vs 179.96&#177;37.40, qingrejiedu: 108.22&#177;36.97 vs 179.96+37.40,and CBP: 91.96&#177;19.0 vs 179.96&#177;37.40, P&lt;0.01) and MDA (20 g/kg WK: 21.6&#177;7.4 vs 48.2&#177;4.5, 10 g/kg WK: 32.2&#177;7.3 vs 48.2&#177;4.5, 5 g/kg WK: 34.2&#177;6.2 vs 48.2+4.5, jianpiyiqi: 34.9&#177;13.8 vs 48.2&#177;4.5, yangxuehuoxue: 35.5&#177;16.7 vs 48.2&#177;4.5, qingrejiedu: 42.2&#177;17.6 vs 48.2&#177;4.5, and CBP: 30.1&#177;6.1 vs 48.2&#177;4.5, P&lt;0.05-0.01) obviously decreased. The 20 g/kg WK group was better than 10 g/kg (the mucus thickness: 51.3&#177;2.9 vs 43.3&#177;2.9, NO: 0.480&#177;0.026 vs 0.390&#177;0.055, SOD: 186.4&#177;19.9 vs 168.2&#177;21.7, P&lt;0.01) and 5 g/kg (the mucus thickness: 51.3&#177;2.9 vs 36.1&#177;7.2, NO: 0.480&#177;0.026 vs 0.394&#177;0.026, SOD: 186.4&#177;19.9 vs 155.6&#177;21.6, P&lt;0.01) groups and CBP group (the mucus thickness: 51.3&#177;2.9 vs 38.2&#177;3.5, NO: 0.480&#177;0.026 vs 0.395&#177;0.053, SOD: 186.4&#177;19.9 vs 156.3&#177;18.1, P&lt;0.01) in the mucus thickness, NO and SOD levels and better than 10 g/kg (86.8&#177;7.6 vs 77.9&#177;7.0, P&lt;0.05) and 5 g/kg (86.8&#177;7.6 vs 70.0&#177;5.4, P&lt;0.05) groups in 6-K-PGF1α level, 10 g/kg WK group was better than 5 g/kg WK (the mucus thickness: 43.3&#177;2.9 vs 36.1&#177;7.2, P&lt;0.01, SOD: 168.2&#177;21.7 vs 155.6&#177;21.6, P&lt;0.05) and CBP groups (the mucus thickness: 43.3&#177;2.9 vs 38.2&#177;3.5, P&lt;0.01, SOD: 168.2&#177;21.7 vs 156.3&#177;18.1, P&lt;0.05) in the mucus thickness and SOD level. In compound group, jianpiyiqi group, yangxuehuoxue group, qingrejiedu group, the level of ET was decreased, NO contents were increased in gastric tissue of ulcers in rats. CONCLUSION: WK decoction and separated recipes have significantly protective effect on ethanol-induced gastric mucosal injury. They can increase the content of EGF in gastric juice, PGI2 SOD in plasma and NO in gastric tissues, thicken the mucus on the gastric mucosa, and decrease the impairing factor MDA, ET in plasma.     

Effects of transmitters and interleukin-10 on rat hepatic fibrosis induced by CCl4

AIM: To study the effects of transmitters ET, AgⅡ, PGI2,CGRP and GG on experimental rat hepatic fbrosis and the antifibrogenic effects of IL-10.METHODS: One hundred SD rats were randomly divided into 3 groups: control group (N): intraperitoneal injection with saline 2 ml.kg^-1 twice a week; the fibrogenesis group (C): intraperitoneal injection with 50 % CC14 2 ml.kg^-1 twice a week; IL-10 treated group (E): besides same dosage of CC14 given, intraperitoneal injection with IL-10 4 ug.kg^-1 from the third week. In the fifth, the seventh and the ninth week,rats in three groups were selected randomly to collect plasma and liver tissues. The levels of ET, AgⅡ, PGI2, CGRP and GG were assayed by radioimmunoassay (RIA). The liver fibrosis was observed with silver staining.RESULTS: The hepatic fibrosis was developed with the increase of the injection frequency of CC14. The ET, AgⅡ, PGI2, CGRP and GG levels in serum of group N were 71.84&#177;60.2 ng.L^-1,76.21&#177;33.3 ng.L^-1, 313.03&#177;101.71 ng.L^-1, 61.97&#177;21.4 ng.L^-1 and 33.62&#177;14.37 ng.L^-1, respectively; the levels of them in serum of group C were 523.30&#177;129.3 ng.L^-1, 127.24&#177;50.0 ng.L^-1,648.91&#177;357.29 ng.L^-1, 127.15&#177;62.0 ng&#183;L^-1 and 85.26&#177;51.83ng.L^-1, respectively; the levels of them in serum of group E were 452.52&#177;99.5 ng.L^-1, 90.60&#177;44.7 ng.L^-1, 475.57&#177;179.70ng.L^-1, 102.2&#177;29.7 ng.L^-1 and 38.05&#177;19.94 ng.L^-1, respectively.The histological examination showed that the degrees of the rats liver fibrosis in group E were lower than those in group C.CONCLUSION: The transmitters ET, AgⅡ, PGI2, CGRP and GG play a significant role in the rat hepatic fibrosis induced by CCl4, IL-10 has the antagonistic action on these transmitters and can relieve the degree of the liver fibrosis.     

Effect of increased hepatic platelet activating factor and its receptor portal hypertension in CCl4-induced liver cirrhosis

AIM: To evaluate the changes in hepatic platelet activating factor (PAF) and its receptors and their effect on portal pressure of cirrhotic rats induced by CCl4. METHODS: A model of liver cirrhosis was replicated in rats by intra-peritoneal injection of CCl4 for 8 wk. We determined the effect of hepatic PAF and its receptor level on portal and arterial pressure by EIA, saturation binding and RT-PCR technique. RESULTS: Compared to control rats, cirrhotic rats had higher hepatic PAF levels and output as well as higher plasma PAF levels (P<0.01, P<0.01, P<0.05, respectively). Both hepatic PAF receptor mRNA levels and PAF binding were nearly 3-fold greater in cirrhotic rats (P<0.01). Portal injection of PAF (1 g/kg WT) increased the portal pressure by 22% and 33% in control and cirrhotic rats, respectively. In contrast, the arterial pressure was decreased in the both groups (54% in control rats and 42% in cirrhotic rats). Injection of the PAF antagonist BN52021 (5 mg/kg WT) decreased the portal pressure by 16% in cirrhotic rats but had no effect in the control rats. CONCLUSION: The upregulation of the PAF system contributes to hepatic hemodynamic and metabolic abnormalities in cirrhosis, and the increased release of PAF into the circulation has impacts on the systemic hemodynamics.     

Effect of ginkgo biloba extract on livers in aged rats

AIM: To investigate the protective effect of ginkgo biloba extract (GBE) on livers of aged rats and the associated mechanisms. METHODS: Two-mo- and 20-mo-old rats were treated with GBE/saline for 3 mo. Liver tissue samples from 5-mo-old rats treated with saline (group Y) and 23-mo-old rats treated with GBE (group E) or saline (group N) were used for histopathological examinations (hematoxylin-eosin and Masson staining, Lipofuscin staining-Schmorl staining) and determination of expression of tissue inhibitor-1 of metalloproteinase (TIMP-1) and the level of malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD). Blood samples were collected for determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and albumin. RESULTS: Microscopic studies with Masson staining revealed mild liver fibrosis in aged rats (group N), while the livers of aged rats receiving GBE (group E) showed amelioration in fibrosis (2.2±0.1 vs2.8±0.1, P＜0.01) and deposition of lipofuscin (33.7±5.3 vs62.8±5.7, P＜0.01). The expression of TIMP-1 and the level of liver MDA (1.0±0.1 vs1.2±0.2,P＜0.05) also decreased but the activity of GPx (97.1±15.3 vs61.8±14.5, P＜0.01) increased in group E. Compared with group Y, the level of liver MDA (0.8±0.1 vs1.2±0.2, P＜0.01), lipofuscin (32.4±6.0 vs 62.8±5.7, P＜0.01) and TIMP-1 expression were increased, while the activity of GPx (103.2±17.6 vs61.8±14.5, P＜0.01) and SOD (16.7±4.4 vs11.8±3.9, P＜0.05) was decreased in group N. There was no difference in liver function among these three groups. CONCLUSION: GBE has protective effects on aging liver. The possible mechanisms might be its antioxidant activity and inhibition of TIMP-1 expression.     

Expression of TNF-α and VEGF in the esophagus of portal hypertensive rats

AIM: To investigate the expression of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) in the development of esophageal varices in portal hypertensive rats. METHODS: Thirty male Sprague-Dawley (SD) rats in the model group in which a two-stage ligation of portal vein plus ligation of the left adrenal vein was performed, were divided into three subgroups (M7, M14, and M21) in which the rats were kiued on the seventh day, the 14^th d and the 21 d after the complete portal ligation. Thirty male SD rats, which underwent the sham operation in the control group, were also separated into three subgroups (C7, C14 and C21) corresponding to the models. The expression of TNF-α and VEGF in the esophagus of all the six subgroups of rats were measured with immunohistochemical SP technique. RESULTS: The portal pressure in the three model subgroups was significantly higher than that in the corresponding control subgroups (23.82&#177;1.83 vs 11.61&#177;0.86 cmH2O, 20.90&#177;3.27 vs 11.43&#177;1.55 cmH2O and 20.68&#177;2.27 vs 11.87&#177;0.79 cmH2O respectively, P&lt;0.01), as well as the number (9.3&#177;1.6 vs 5.1&#177;0.8, 11.1&#177;0.8 vs 5.4&#177;1.3 and 11.7&#177;1.5 vs 5.2&#177;1.1 respectively, P&lt;0.01) and the total vascular area (78 972.6&#177;3 527.8 vs 12 993.5&#177;4 994.8 um^2, 107 207.5&#177;4 6461.4 vs 11 862.6&#177;5 423.2 um^2 and 110 241.4&#177;49 262.2 vs 11 973.7&#177;3 968.5 um^2 respectively, P&lt;0.01) of submucosal veins in esophagus. Compared to the corresponding controls, the expression of TNF-α and VEGF in M21 was significantly higher (2.23&#177;0.30 vs 1.13&#177;0.28 and 1.65&#177;0.38 vs 0.56&#177;0.30 for TNF-α and VEGF respectively, P &lt;0.01), whereas there was no difference in M7 (1.14&#177;0.38 vs 1.06&#177;0.27 and 0.67&#177;0.35 vs 0.50&#177;0.24 for TNF-α and VEGF respectively, P&gt;0.05) and M14 (1.20&#177;0.25 vs 1.04&#177;0.26 and 0.65&#177;0.18 vs 0.53&#177;0.25 for TNF-α and VEGF respectively, P&gt;0.05). And the expression of TNF-α and VEGF in M21 was significantly higher than that in M7 (2.23&#177;0.30 vs 1.14&#177;0.38 and 1.65&#177;0.38 vs 0.67&#177;0.35 for TNF-α and VEGF respectively, P&lt;0.01) and M14 (2.23&#177;0.30 vs 1.20&#177;0.25 and 1.65&#177;0.38 vs 0.65&#177;0.18 for TNF-α and VEGF respectively, P&lt;0.01), but there was no difference between M7 and M14 (1.14&#177;0.38 vs 1.20&#177;0.25 and 0.67&#177;0.35 vs 0.65&#177;0.18 for TNF-α and VEGF respectively, P &gt;0.05). CONCLUSION: In the development of esophageal varices in portal hypertensive rats, increased TNF-α and VEGF may be not an early event, and probably play a role in weakening the esophageal wall and the rupture of esophageal varices.     

应激状态下胃黏膜屏障变化的实验研究

目的　观察应激状态下胃黏膜屏障的变化。方法　 80只大鼠随机分为A、B及C组 ,其中A组分为单纯应激组和应激加奥美拉唑组 ,测定胃酸和胃碱分泌的变化 ;B组分为正常对照组、应激 1、2、4h组 ,测定胃壁结合黏液量、凝胶层厚度和制备硝酸镧标记胃黏膜标本 ;C组的分组与A组相同 ,用于测定胃腔内H+ 丢失量。以水浸束缚方法制备应激模型。结果　A组胃酸分泌呈增高趋势 ,胃碱分泌呈下降趋势。B组胃壁结合黏液量 (A/g)分别为 0 137± 0 0 30、0 14 3± 0 0 12、0 0 6 6± 0 0 16、0 0 16± 0 0 16 ;凝胶层厚度 (μm)分别为 71 0 8± 5 85、74 5 0± 12 85、5 7 6 3± 6 4 5、5 1 35± 2 84。应激 2、4h组显著低于对照组及应激 1h组 (P <0 0 1)。对照组胃黏膜上皮细胞间未见硝酸镧标记 ,应激组普遍见有硝酸镧标记。C组单纯应激组大鼠应激 5h内每小时胃腔内H+ 丢失量 (μmol)分别为 2 0 3±0 12、2 0 0± 0 2 0、1 93± 0 4 9、2 70± 0 4 4、3 37± 0 35 ,应激 3h后H+ 丢失量逐渐增加 (P <0 0 1) ;应激加奥美拉唑组H+ 丢失量 (μmol)分别为 7 4 6± 1 2 2、4 5 6± 0 35、3 11± 0 81、2 32± 1 4 2、2 13± 1 6 0 ,H+ 丢失量逐步降低 (P <0 0 5 ) ,应激 3h内各时段H+ 丢失量显著高