Effects of long-term tea polyphenols consumption on hepatic microsomal drug-metabolizing enzymes and liver function in Wistar rats

AIM: To investigate the effects of long-term tea polyphenols (TPs) consumption on hepatic microsomal drug-metabolizing enzymes and liver function in rats.METHODS: TPs were administered intragastrically to rats at the doses of 833 mg.kg-1.d-1 (n=20) and 83.3 mg.kg-1@d-1 (n=20) respectively for six months. Controlled group (n=20)was given same volume of saline solution. Then the contents of cytochrome P450, bS, enzyme activities of aminopyrine N-demethylase (ADM), glutathione S-trasferase (GST) and the biochemical liver function of serum were determined.RESULTS: The contents of cytochrome P450 and b5 in the livers of male rats in high dose groups (respectively 2.66±0.55,10.43±2.78 nmol.mg MS pro-1) were significantly increased compared with the control group (1.08±1.04, 5.51±2.98nmol.mg MS pro-1; P＜0.01, respectively). The enzymatic activities of ADM in the livers of female rats in high dose groups (0.91±0.08 mmol@mg MS pro-1min-1) were increased compared with the control group (0.82±0.08 mmol.mg MS pro-1.min-1; P＜0.05). The GST activity was unchanged in all treated groups, and the function of liver was not obviously changed.CONCLUSION: The antidotal capability of rats' livers can be significantly improved after long-term consumption of TPs.There are differences in changes of drug-metabolizing enzymes between the sexes induced by TPs and normal condition.     

Protective effect of doxorubicin induced heat shock protein 72 on cold preservation injury of rat livers

AIM:To observe the protective effect of heat shock protein72 (HSP 72) induced by pretreatment of doxorubicin (DXR)on long-term cold preservation injury of rat livers.METHODS:Sprague-Dawley rats were administeredintravenously DXR at a dose of 1mg/kg body mass in DXRgroup and saline in control group.After 48h,the rat liverwas perfused with cold Linger's and University of Wisconsin(UW) solutions and then was preserved in UW solution at4℃ for 24,36 and 48 h.AST,ALT,LDH and hyaluronic acidin preservative solution were determined.Routine HE,immunohistochemical staining for HSP 72 and electronmicroscopic examination of hepatic tissues were performed.RESULTS:After 24,36 and 48 h,the levels of AST,ALTand hyaluronic acid in preservative solution were significantlyhigher in control group than in DXR group (P<0.05),whileLDH level was not significantly different between the 2 groups(P>0.05).Hepatic tissues in DXR group were morphologicallynormal and significantly injured in control group.HSP 72was expressed in hepatocytes and sinusoidal endothelialcells in DXR group but not in control group.CONCLUSION:Pretreatment of DXR may extend the time ofrat liver cold preservation and keep liver alive.The expressionof HSP 72 in liver can prevent hepatocytes and sinusoidalendothelial cells from long-term cold preservation injury.     

Protective effect of doxorubicin induced heat shock protein 72 on cold preservation injury of rat livers

AIM: To observe the protective effect of heat shock protein 72 (HSP 72) induced by pretreatment of doxorubicin (DXR) on long-term cold preservation injury of rat livers.METHODS: Sprague-Dawley rats were administered intravenously DXR at a dose of 1 mg/kg body mass in DXR group and saline in control group. After 48 h, the rat liver was perfused with cold Linger‘s and University of Wisconsin (UW) solutions and then was preserved in UW solution at 4℃ for 24, 36 and 48 h. AST, ALT, LDH and hyaluronic acid in preservative solution were determined. Routine HE,immunohistochemical staining for HSP 72 and electron microscopic examination of hepatic tissues were performed.RESULTS: After 24, 36 and 48 h, the levels of AST, ALT and hyaluronic acid in preservative solution were significantly higher in control group than in DXR group (P&lt;0.05), while LDH level was not significantly different between the 2 groups (P&gt;0.05). Hepatic tissues in DXR group were morphologically normal and significantly injured in control group. HSP 72 was expressed in hepatocytes and sinusoidal endothelial cells in DXR group but not in control group.CONCLUSION: Pretreatment of DXR may extend the time of rat liver cold preservation and keep liver alive. The expression of HSP 72 in liver can prevent hepatocytes and sinusoidal endothelial cells from long-term cold preservation injury.     

Effect of L—NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats

AIM: To invsstigare the effect of L-NAME on nitric oxide andgastriubtestubal motility alterations in cirrhotic ratsMETHODS: Rats with cirrhosis induced by carbontetrachloride were randomly divided into two groups, one( n= 13) receiving 0. 5 mg@ kg-1 per clay of NG-nitro-L-argininemethyl ester (L-NAME), a nitric oxide synthase inhibitor,for 10 days, whereas the other group ( n = 13) and control( n = 10) rats were administrated the same volume of 9 g@ L-1saline.Half gastric emptying time and 2 h residual rate weremeasured by SPECT, using 99m Tc-DTPA-labeled bariumsuifate as test meal. Gastrointestinal transition time wasrecorded simultaneously. Serum concentration of nitrcoxide (NO) was determined by the kinetic cadmiunreduction and colorimetric methods. ImmunohistochemicalSABC method was used to observe the expression anddistribution of three types of nitric oxide synthase (NOS)isoforms in the mt gastrointestinal tract. Western blot wasused to detect expression of gastrointestinal NOS isoforms.RESULTS: Half gastric emptying time and trans-gastrointestinal time were significantly prolonged( 124.0 ± 26.4min; 33.7± 8.9min;72.1 ± 15.3 min; P＜0.01), (12.4±0.5h; 9.5±0.3 h; 8.2±0.8 h; P＜0.01), 2h residual rate wasraised in cirrhotic rots than in controls and cirrhotic ratstreated with L-NAME(54.9± 7.6 % ,13.7 ± 3.2 %, 34.9± 10.3%, P＜ 0.01). Serum concentration of NO was significantlyincreased in cirrhotic rots than in the other groups (8.20 ± 2.48)μmol@L-1, (5.94± 1.07) μmol@L-1 ,and control (5.66± 1.60) tμmol@L-1, P＜ 0.01. NOS staining intensities which weremainly located in the gastrointestinal tissues were markedlylower in cirrhotic rats than in the controls and cirrhotic ratsafter treated with L- NAME.CONCLUSION: Gastrointestinal motility was remarkablyinhibited in cirrhotic rats, which could he alleviated by L-NAME. Nitric oxide may play an important role in theinhibition of gastrointestinal motility in cirrhotic rats.     

Peroxisome proliferator activated receptor-y in pathogenesis of experimental fatty liver disease

AIM:To study the expression of peroxisome proliferatoractivated receptor-γ(PPARγ) in the liver of rats with fattyliver disease (FLD) and to explore the role of PPARγ in thepathogenesis of FLD to provide the basis for using PPARγligand to treat patients with FLD.METHODS:Forty Wistar rats were divided into 4 groupsof ten rats each randomly:normal group (group A),alcoholgroup (group B),fat-rich diet group (group C),alcohol andfat-rich diet group (group D).The rats were sacrificed atthe end of the 16th week from the feeding day.Alanineaminotransferase (ALT),tumor necrosis factor-alfa (TNFα)in serum and malondialdehyde (MDA) in liver homogenatewere determined;livers were collected for observingpathologic changes by HE,Sudan Ⅳ,Masson stain undermicroscope.The morphologic results were analyzed bypicture quantitative analysis technique.The changes ofultrastructure were also examined under electron microscope.The expression of PPARγ in liver was detected by immunoh-istochemistry and RT-PCR.The correlations between theexpression of PPARy and biochemical indexes,and liverhistology were analyzed.RESULTS:The steatosis,inflammation,necrosis and fibrosiswere present in livers of different experimental groups,especially in livers of alcohol and fat-rich diet group.Thecontent of immunodetectable PPARγ was decreasedremarkably in the livers of model rats (group B-D);the levelin alcohol and fat-rich diet group (3.43±1.48) was significantlylower than that in normal group (18.34±3.73),alcohol group(8.82±2.52) and fat-rich diet group (11.73±2.51) (all P<0.01).The level of PPARγ mRNA was also lower in the livers ofmodel rats (group B-D) than in livers of controls.Theexpression of PPARγ in rat liver correlated negatively withthe degree of its inflammation,necrosis and fibrosis,aswell as the level of serum TNFα and the content of MDA inliver homogenates,but not with steatosis or serum ALT.CONCLUSION:Decreased expression of PPARγ may playan important role in the development of hepatocellularinflammation,necrosis and fibrosis of rats with FLD.Thus,activating PPARγ by its ligand can be anticipated to providea therapy target for FLD.     

Expression and significance of HIF-1α and VEGF in rats with diabetic retinopathy

Objective:To investigate the expression of hypoxia inducible iaclor-1α(HIF-1α)and vascular endothelial growth factor(VECF)in diabelic retinopathy(DR)rats and its effect on the DR occurrence and development.Methods:A total of 120 SD rats were randomly divided into trial group and control group with 60 in each.STZ.i.p.was used in the trial group to establish the DM model,citrate buffer salt of same amount was used up.to the control group.1,3 and 6 months after injection,respective 20 rats were sacrificed in each group to observe expression of HIF-1αand VEGF in the rat retina tissue at different lime points.Results:Expression of HIF-1αand VEGF were negative in the control group;expression of HIF-1αand VKGF protein in retinal tissue were weak after 1 month of DR mold formation.It showed progressive enhancement along with the progression in different organizations,differences between groups were significant(P0.05).Conclusions:Expressions of HIF-1αand VF.GF were;correlated with disease progression in early diabelic relinopathy.Retinal oxygen can induce over-expression of HIF-1αand VEGF.It shows that HIF-1αand VEGF play an important role in the pathogenesis of DR.     

己酮可可碱对非酒精性脂肪肝大鼠肝组织线粒体解耦联蛋白表达的影响

Objective To investigate the effects of pentoxifylline (PTX) on the expression of uncoupling protein 2 (UCP-2) of hepatic mitochondria in rats with nonalcoholic fatty liver disease (NAFLD). Methods Sixty SD rats were randomly divided into 3 groups (each n = 20): normal control group, experiment group and treatment group. The rats in normal control group were given a normal feed. The rats in experiment and treatment groups were given fat-rich feed. Furthermore, the rats in treatment group were given PTX after 4 weeks in fat-rich diet feeding. The expression of UCP-2 in the liver was detected by immunohistochemistry and semi-quantitative RT-PCR. Results The hepatic expression of UCP2 mRNA was higher in experiment group (4.0±0.3) than in normal control group (1.2±0.1). The hepatic expression of UCP2 mRNA was higher in treatment group (3.0±0.2) than in normal control group, but the hepatic expression of UCP2 mRNA was lower in treatment group than in experiment group (F = 160. 67, P＜ 0. 01). Conclusions The UCP-2 mRNA is expressed in livers of NAFLD, pentoxifylline plays an important role in the reduction of expression of UCP-2 mRNA in lives of NAFLD.     

Expression of macrophage inflammatory protein-1α in alveolar macrophage in rat subjecting mechanical ventilation

Objective To explore the role of alveolar macrophage(AM)activation in ventilator induced lung injury(VILI)by measuring macrophage inflammatory protein-1α(MIP-1α)and nuclear factorkappa B(NF-κB)p65 expressed in AM of rats with different tidal volume ventilations.Methods Thirty-two male Wistar rats were randomly divided into four groups:control group,low tidal volume group,conventional tidal volume group and high tidal volume group.The levels of MIP-1α and NF-κB p65 expressed in AM in BALF were measured by SABC method respectively and the ultrastructures of AM were observed with 100-CX transmission electron microscope.Results The percentages of AM in BALF stained positively with MIP-1α and NF-κB p65 both in high and conventional tidal volume groups were significantly higher than those in control and low tidal volume groups(P＜0.01).The percentages of AM in BALF stained positively with MIP-1α and NF-κB p65 in high tidal volume group were also significantly higher than those in conventional tidal volume group(P＜0.05),but no statistical differences existed between low tidal volume group and control group.Under transmission electron microscope the AM in high and conventional tidal vol ume groups appeared in active state.Conclusions AM is one of the starting cells to inducing VILI and plays an important role in VILI.AM activation and releasing MIP-1α is one of the main reasons leading to neutrophils aggregated and activated in the lungs and so to developing VILI.AM expression and releasing MIP-1α may be regulated by NF-κB to some extent.     

Apoptosis induced by a low-carbohydrate and high-protein diet in rat livers

AIM: To determine whether high-protein, high-fat, and low-carbohydrate diets can cause lesions in rat livers.METHODS: We randomly divided 20 female Wistar rats into a control diet group and an experimental diet group. Animals in the control group received an AIN-93 M diet, and animals in the experimental group received an Atkins-based diet(59.46% protein, 31.77% fat, and 8.77% carbohydrate). After 8 wk, the rats were anesthetized and exsanguinated for transaminases analysis, and their livers were removed for flow cytometry, immunohistochemistry, and light microscopy studies. We expressed the data as mean ± standard deviation(sd) assuming unpaired and parametric data; we analyzed differences using the student's t-test. statistical significance was set at P 0.05.RESULTS: We found that plasma alanine aminotransferase and aspartate aminotransferase levels were significantly higher in the experimental group than in the control group. According to flow cytometry, the percentages of nonviable cells were 11.67% ± 1.12% for early apoptosis, 12.07% ± 1.11% for late apoptosis, and 7.11% ± 0.44% for non-apoptotic death in the experimental diet group and 3.73% ± 0.50% for early apoptosis, 5.67% ± 0.72% for late apoptosis, and 3.82% ± 0.28% for non-apoptotic death in the control diet group. The mean percentage of early apoptosis was higher in the experimental diet group than in the control diet group. Immunohistochemistry for autophagy was negative in both groups. sinusoidal dilation around the central vein and small hepatocytes was only observed in the experimental diet group, and fibrosis was not identified by hematoxylin-eosin or Trichrome Masson staining in either group.CONCLUSION: Eight weeks of an experimental diet resulted in cellular and histopathological lesions in rat livers. Apoptosis was our principal finding; elevated plasma transaminases demonstrate hepatic lesions.     

Effect of Maotai liquor in inducing metallothioneins and on hepatic stellate cells

AIM：To explore the possible mechanism why drinking Maotai liquor dose not cause hepatic fibrosis.METHODS:After being fed with Maotai for 56 days consecutively,the male SDrats were decollated for detecting the biological indexes,and the livers were harvested to examine the liver indexes and the level of hepatic metallothioneins(MT),Hepatic stellate cells(HSC) proliferation and collagen generation were also observed.RESULTS:Hepatic MT contents were 216.0ng.g^-1&#177;108ng.g^-1 in the rats of Maotai group and 10.0ng.g^-1&#177;2.8ng.g^-1 in the normal control group,which was increased obviously in Maotain group(P&lt;0.05),In the rate with grade CCL2 Poisoning induced by Maotai,epatic MT content was 304.8ng.g^-1&#177;12.1ng.g^-1 whereas in the controls with grade CCL4 posoing,it was 126.4ng.g^-1&#177;4.8ng.g^-1(P&lt;0.05),MDA was 102.0nmol.g^-1&#177;3.4nmol.g^-1 in Maotai group and 150.8nmol.g&#177;6.7nmol.g^-1 in the control group(P_&lt;0.05),When both of the groups were suffering from grade CCL4 poisoning,hepatic MT contents was negatively correlated with MDA(r=-0.8023,n=20,P&lt;0.01),The 570 nmA values of each tube with HSC regeneration at concentrations of 0,10,50,100,and 200g.L^-1 of Maotai were 0.818,0.742,0.736.0.72,0.682,and 0.604,respectively.From the concentration of 10g.L^-1,Maotai began to show obvious inhibitory effcets against HSC,and the inhibition was concentration-dependent (P&lt;0.05,P&lt;0.01).Type I Collagen contents in HSC were 61.4,59.9,50.1,49.2,48.7,34.4μg&#183;^-1at concentrations of 0,10,50,100,and 200g.L^-1 of Maotai .At the concentration of 100-200 g.L^-1,Matotai had obvious inhibitory effect against the secretion of type I collagen(P&lt;0.05).Gene expression analysis was conducted on celss with Maotai Concentrations of 0,50,100g.L^-1 respectively and the ash valuse of β-actin gene expression were 0.88,0.74,and 0.59,respectively,suggesting that at the concentration of 100g.L^-1 Maotal could obviously inhibit gene expression of type I procollagen (P&lt;0.05),but the effect was not obvious at the concentration of 50g.L^-1(P&gt;0.05),At the concentration of 10g.L^-1 HSC growth in vitro inhibition rates were 16.4&#177;2.3 in Maotai group and -8.4&#177;2.3 in the control group(P&lt;0.05) CONCLUSION:Maotai liquor can increase metallothioneins in the liver and inhibit the activation of HSC and the synthesis of collagen in many aspects,which might be the mechanism that Maotal liquor interferes in the hepatic fibrosis.     

Exercise-induced apoptosis of rat skeletal muscle and the effect of meloxicam

The aim of this study was to evaluate the effect of exercise on apoptosis in rat gastrocnemius and soleus muscle tissue and to determine the effect of meloxicam, a novel non-steroidal anti-inflammatory drug (NSAID), on the ratio of exercise-induced apoptosis. Forty male Wistar rats were used in the experiments. Spontaneous wheel-running was used as an exercise protocol. Rats were divided randomly into four groups. Group A (n = 10) was the control group, in which rats did not perform any exercise. In group B (n = 10), gastrocnemius and soleus muscles were biopsied immediately after exercise. The rats in group C (n = 10) were placed back in their cages after exercise and allowed to rest for 48 h, after which the gastrocnemius and soleus muscles were biopsied. In group D (n = 10), rats were given 11 mg meloxicam (Mobic, Boehringer Ingelheim) per kilogram body weight per day p.o. for 2 days, after which gastrocnemius and soleus muscles were biopsied 48 h after exercise. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labelling (TUNEL) technique was used to detect DNA fragmentation in situ. TUNEL-positive nuclei were identified and counted. The apoptosis ratio in gastrocnemius muscle was 0.50x10(-3)+/-0.96x10(-3) in group A, 5.42x10(-3)+/-3.58x10(-3) in group B, 3.55x10(-3)+/-3.23x10(-3) in Group C and 3.52x10(-3)+/-1.00 in Group D; the ratios in soleus muscle were 0.98x10(-3)+/-1.83x10(-3), 3.03x10(-3)+/-2.78x10(-3), 4.48x10(-3)+/-3.32x10(-3) and 2.91x10(-3) 1.98x10(-3), respectively. The differences between the apoptosis ratios in group A and B, Group A and C, and Group A and D were statistically significant (P < 0.05). There was no statistically significant difference between group C and D. In conclusion, exercise increased apoptosis in gastrocnemius and soleus muscle tissue, and the apoptosis ratios were not affected by meloxicam.     

Antitumor immunity induced by DNA vaccine encoding alpha-fetoprotein／heat shock protein 70

AIM:To construct a DNA vaccine encoding human alpha-fetoprotein (hAFP)/heat shock protein 70 (HSP70), and to study its ability to induce specific CTL response and its protective effect against AFP-expressing tumor.METHODS: A DNA vaccine was constructed by combiningh AFP gene with HSP70 gene. SP2/0 cells were stably transfected with pBBS212-hAFP and pBBS212-hAFP/HSP70 eukaryotic expression vectors. Mice were primed and boosted with DNA vaccine hAFP/HSP70 by intramuscular injection, whereas plasmid with hAFP or HSP70 was used as controls. ELISPOT and ELISA were used to detect IFN-γ-producing splenocytes and the level of serum anti-AFP antibody from immunized mice respectively. In vivo tumor challenge was measured to assess the immune effect of the DNA vaccine.RESULTS: By DNA vaccine immunization, the results of ELISPOT and ELISA showed that the number of IFN-γ-producing splenocytes and the level of serum anti-AFP antibody were significantly higher in rhAFP/HSP70 group than in hAFP and empty plasmid groups (95.50&#177;10.90 IFN-γ spots/10^6 cells vs 23.60&#177;11.80 IFN-γ spots/10^6 cells,7.17&#177;4.24 IFN-γ spots/106 cells, P&lt;0.01; 126.50&#177;8.22μg/mL vs 51.72&#177;3.40μg/mL, 5.83&#177;3.79μg/mL, P&lt;0.01). The tumor volume in rhAFP/HSP70 group was significantly smaller than that in pBBS212-hAFP and empty plasmid groups (37.41&#177;7.34 mm^3 vs 381.13&#177;15.48 mm^3, 817.51&#177;16.25 mm^3,P&lt;0.01). CONCLUSION: Sequential immunization with a recombinant DNA vaccine encoding AFP and heat shock protein70 could generate effective AFP-specific T cell responses and induce definite antitumor effects on AFP-producing tumors, which may be suitable for some clinical testing as a vaccine for HCC.     

Ultrasound guided percutaneous cholecystostomy in high-risk patients for surgical intervention

INTRODUCTION Cholecystectomy is the appropriate treatment of acute calculous and acalculous cholecystitis, and it has a mortal- ity rate of 0%-0.8%[1,2]. However, the mortality rate of surgical treatment may be as high as 14%-30% in elderly or critically ill patients with comorbid diseases[3,4]. Percutaneous cholecystostomy (PC) has been intro- duced as an alternative method to treat acute cholecystitis in patients with significant comorbid diseases[5-8]. PC can be achieved with the guid…     

Epidemiological and histopathological study of relevance of Guizhou Maotai liquor and liver diseases

AIM：To explore the relevance of Maotai liquor and liver diseases.METHODS:Epidemiological study was conducted on groups of subjects,each consisting of 3 subjects from the Maotai liquor roup consisting of 99 individuals and one from the non-alcoholic control group consisting of 33 individuals Liver biopsy was performed on 23 volunteere from Guizhou Maotai Distillery who had a constant and long history of drinking Maotai liquor.Experimental histopathological study was conducted as follows:Sixty male Wistar rate were divided into 3 groups randomly and fed with Maotai liquor,ordinary white wine,and physiological saline respectively for a period of 8and 12 weeks,The rats were sacrificed in batches,then serum ALT,AST,TBil,and AKP were measured.Rat livers were harvested to Measure the liver indexes GSH,and MDA.Histopathological examinations were also performed.Another eighty mice were randomly divided into 4 groups and fed with Maotai(at different dosages of 10ml.kg^-1 and 20ml.kg^-1),ethanol,and physiological saline.The animals were sacrificed after 4 weeks and serum ALT was determined ,Then the livers were harvested and liver indexes and MDA were measured.RESULTS:The incidence rate of hepatic symptoms splenomegaly,liver function impairment,reversal of Albumin/Globulin and increased diameter of portal verins in the Maotai liquor group were 1.0%(1/99),1.0%(1/99),1.0%(1/99),1.0%(1/99),9(9/99)and 9(0/99),0(0/99),0(0/99),0(0/99),0(0/99),respectively,There was no significant difference between the Maotai group[ and the non-alcoholic control group(P&gt;0\05),Various degree of fatty infiltration of hepatocytes was found in the 23 volunteers receiving liver biopsy.but there was no obvious hepatic fibrosis or cirrhosis.A comparison was made between the Maotai liquor group and the ordinary white wine group,It was found that hepatic MAD in rats and mice,were 0.33&#177;0.10and 0.49&#177;0.23respectively in Maotai group and 0.61&#177;0.22and 0.66&#177;0.32inthe ordinary white wine group;MDA had an obvious decrease in the Maotai liquor group(P&lt;0.05)hepatic GSH were 0.12mg.g^-1&#177;0.06mg.g^-1 in rats of the Maotai liquor group and (0.08&#177;0.02)mg.g^-1 in white wine group,it was obviously increased in the Maotai liquor group(P&lt;0.05),Atfer the 20 rats had been fed with ordinary white wine for 8 Weeks consecutively,disarranged hepatocyte cords,fatty infiltration of hepatocytes,and fibrous septa of varying widths due to hepatic connective tissues proliferation were observed;after 12 weeks,the fibrous tissue proliferation continued and early cirrhosis appeared.COmpared with the ordinary whtite wine group fatty infiltration was observed in the 8-week and 12-week groups,but no necrosis or filbrosis or cirrhosis was found in the Maotai liquor group(P&lt;0.05）。CONCLUSION:Maotai liquor may cause fatty liver but not hepatic fibrosis or cirrhosis,and it can strengthen lipid peroxidation in the liver。     

Effect of bowel rehabilitative therapy on structural adaptation of remnant small intestine: animal experiment

AIM To investigate the individual and thecombined effects of glutamine, dietary fiber,and growth hormone on the structural adaptationof the remnant small bowel.METHODS Forty-two adult male Sprague-Dawley rats underwent 85% mid-small bowelresection and received total parenteral nutrition(TPN) support during the first threepostoperational days. From the 4thpostoperational day, animals were randomlyassigned to receive 7 different treatments for 8days: TPNcon group, receiving TPN and enteral20g·L~1 glycine perfusion; TPN Gin group,receiving TPN and enteral 20 g·L~1 glutamineperfusion; ENcon group, receiving enteralnutrition (EN) fortified with 20 g·L~1 glycine; EN Gin group, enteral nutrition fortified with20g·L~1 glutamine; EN Fib group, enteralnutrition and 2 g·d~1 oral soybean fiber; EN GHgroup, enteral nutrition and subcutaneousgrowth hormone (GH) (0. 3IU) injection twicedaily; and ENint group, glutamine-enriched EN,oral soybean fiber, and subcutaneous GHinjection.RESULTS Enteral glutamine perfusion duringTPN increased the small intestinal villus height(jejunal villus height 250μm 29μm in TPNcon vs 330μm±54μm in TPN Gln, ileal villus height260μm±28μm in TPNcon vs 330μm±22μm inTPN Gln, P<0.05) and mucosa thickness(jejunal mucosa thickness 360μm ± 32μm inTPNcon vs 460μm±65μm in TPN Gln, ilealmucosa thickness 400μm ± 25μm in TPNcon vs490μm ± 11μm in TPN Gin, P<0.05) incomparison with the TPNcon group. Either fibersupplementation or GH administration improvedbody mass gain (end body weight 270 g ± 3.6 g inEN Fib, 265.7 g ± 3.3 g in EN GH, vs 257g±3.3g in ENcon, P<0.05), elevated plasmainsulin-like growth factor (IGF-I) level(880μg·L~1±52μg.L~(-1) in EN Fib, 1200μg·L(-1) 96μg·L~(-1) in EN GH, vs 620μg·L~(-1) ±43μg·L~1 in ENcon, P<0.05), and increased thevillus height (jejunum 560μm ± 44μm in EN ± Fib,530μm ± 30μm in EN±GH, vs 450μm±44μm inENcon, ileum 400μm ± 30μm in EN Fib, 380μm±49μm in EN ± GH, vs 320μm ± 16μm in ENcon,P<0.05) and the mucosa thickness (jejunum740μm ± 66μm in EN ± Fib, 705μm ± 27 μm in EN ±GH, vs 608μm ± 58μm in ENcon, ileum 570μm ±27μm in EN ± Fib, 560μm ± 56μm in EN ± GH, vs480μm ± 40μm in ENcon, P<0.05) in remnantjejunum and ileum. Glutamine-enriched ENproduced little effect in body mass, plasma IGF-I level, and remnant small bowel mucosalstructure. The ENint group had greater bodymass (280g ± 2.2 g), plasma IGF-1 level(1450μg.L~1 ± 137μg.L~1), and villus height(jejunum 620μm ± 56μm, ileum 450μm ± 31μm)and mucosal thickness (jejunum 800μm ± 52μm,ileum 633μm ± 33μm) than those in ENcon, EN Gln (jejunum villus height and mucosa thickness450μm ± 47μm and 610μm ± 63μm, ileum villusheight and mucosa thickness 330μm ± 39μm and500μm±52μm), EN GH groups (P<0.05), andthan those in EN Fib group although nostatistical significance was attained.CONCLUSION Both dietary fiber and GH whenused separately can enhance the postresectionalsmall bowel structural adaptation. Simultaneoususe of these two gut-trophic factors can producesynergistic effects on small bowel structuraladaptation. Enteral glutamine perfusion isbeneficial in preserving small bowel mucosalstructure during TPN, but has little beneficialeffect during EN.     

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.     

急性肝功能衰竭大鼠内毒素血症对肝脏和肾脏糖异生功能的影响

目的探讨大鼠急性肝功能衰竭时内毒素血症对肝脏及肾脏糖异生功能及血糖水平的影响。方法24只雄性健康成年SD大鼠,随机分成4组,每组6只,Ⅰ组：腹腔注射等渗盐水,Ⅱ组：腹腔注射400 mg/kg D-氨基半乳糖（D-GaLN）;Ⅲ组：腹腔注射400 mg/kg D- GaLN＋50μg/kg LPS,Ⅳ组：腹腔注射400 mg/kg D-GaLN＋500μg/kg LPS。LPS注射后6 h,取血清检测内毒素、肾功能,取大鼠肝组织及肾组织,采用荧光定量PCR方法检测磷酸烯醇丙酮酸磷酸羧激酶（PEPCK）基因表达。结果Ⅰ组、Ⅱ组大鼠未见明显的内毒素血症,Ⅲ组、Ⅳ组大鼠体内内毒素水平明显升高,Ⅳ组高于Ⅲ组（8.05±0.43对比3.50±2.25,P〈0.05）。Ⅰ组、Ⅱ组、Ⅲ组大鼠于LPS注射前后未出现低血糖,Ⅳ组大鼠于LPS注射后6h出现明显的低血糖。各组大鼠肾功能均在正常水平,仅有Ⅳ组大鼠出现血清尿素氮水平轻度增高。大鼠肝脏PEPCK的表达在Ⅰ组、Ⅱ组、Ⅲ组、Ⅳ组逐渐减少,差异有统计学意义（2.54±1.32、1.87±0.15、0.91±0.13、0.44±0.42,P〈0.05）;大鼠肾脏PEPCK的表达,同Ⅰ组比较,Ⅱ组无明显变化（0.75±0.03对比0.77±0.04,P〉0.05）,Ⅲ组明显增强（0.75±0.03对比1.63±0.86,P〈0.05）,Ⅳ组大鼠肾脏PEPCK表达显著减弱（0.75±0.03对比0.13±0.07,P〈0.05）。结论急性肝功能衰竭大鼠中严重的内毒素血症通过抑制PEPCK的转录损伤肝脏和肾脏糖异生的功能,导致低血糖的发生。     

非酒精性脂肪性肝病大鼠肝脏解偶联蛋白2表达及其与能量贮备的关系

目的探讨非酒精性脂肪性肝病(NAFLD)大鼠肝脏线粒体解偶联蛋白2(UCP2)表达及其与能量贮备的关系。方法模型组SD大鼠给予高脂肪高胆固醇饮食饲养,分批于实验第8、12、16、24 周处死,同期设普通饮食饲养大鼠作对照。免疫组织化学和逆转录聚合酶链反应(RT-PCR)检测肝脏UCP2 mRNA转录及其蛋白表达。荧光测定法检测肝脏三磷酸腺苷(ATP)含量。结果模型组大鼠8周呈现单纯性脂肪肝,12-24周从脂肪性肝炎进展为脂肪性肝炎伴肝纤维化。免疫组织化学和RT-PCR显示,随着造模时间延长,模型组肝脏UCP2表达逐渐增强,UCP mRNA转录于24周达高峰,较对照组升高4.2倍, t=16.474,P<0.01;模型组肝脏ATP含量则随造模时间延长而逐渐减低,24周为(1.99±0.66) ×108μmol/g,对照组为(2.97±0.48)×108μmol/g,t=3.248,P<0.01。模型组肝脏UCP2 mRNA 转录的相对数值与其ATP含量呈密切负相关,r=-0.93,P<0.01。结论持续24周高脂饮食成功复制大鼠NAFLD模型,模型大鼠肝脏UCP2表达增强而ATP含量减少,两者之间关系密切。