Key factors in developing the trinitrobenzene sulfonic acid-induced post-inflammatory irritable bowel syndrome model in rats

AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following conditions:(1)with different doses(20,10,5 mg/0.8 mL per rat);(2)with same dose in different concentrations(20 mg/rat,25,50 mg/mL);(3)in different ethanol percentage(25%,50%);and(4)at depth either 4 cm or 8 cm from anus.At 5 d and 4 wk after TNBS administration,inflammation severity and inflammation resolution were evaluated.At 4 and 8 wk after TNBS application,visceral hyperalgesia and enterochromaffin(EC)cell hyperplasia were assayed by abdominal withdrawal reflex test,silver staining and capillary electrophoresis. RESULTS:Our results showed that:(1)TNBS induced dose-dependent acute inflammation and inflammation resolution.At 5 d post TNBS,the pathological score and myeloperoxidase(MPO)activity in all TNBS treated rats were significantly elevated compared to that of the control(9.48±1.86,8.18±0.67,5.78± 0.77 vs 0,and 3.55±1.11,1.80±0.82,0.97±0.08 unit/mg vs 0.14±0.01 unit/mg,P0.05).At 4 wk post TNBS,the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control(1.52±0.38 and 0.80±0.35 vs 0,P0.05);(2)Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia.At 4 wk post TNBS,abdominal withdrawal reflex (AWR)threshold pressure in all TNBS-treated groups were decreased compared to that of the control(21.52 ±1.73 and 27.10±1.94 mmHg vs 34.44±1.89 mmHg,P0.05).At 8 wk post TNBS,AWR threshold pressure in 8 cm administration group was still significantly decreased(23.33±1.33 mmHg vs 36.79±2.29 mmHg,P0.05);(3)Ethanol percentage affected the TNBS-induced inflammation severity and visceral hyperalgesia.In TNBS-25%ethanol-treated group,the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50%ethanoltreated group,while AWR threshold pressure were significantly elevated(36.33±0.61 mmHg vs 23.33±1.33 mmHg,P0.05);and(4)TNBS(5 mg/0.8 mL per rat, in 50%ethanol,8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.CONCLUSION:TNBS dosage,concentration,intraco-lonic administration position,and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats.     

Involvement of parasympathetic pelvic efferent pathway in psychological stress-induced defecation

AIM:To investigate the role of the pelvic nerve pathway in stress-induced acceleration of colorectal transit and defecation in rats.METHODS:Surgical transection of rectal nerves(rectal branches of the pelvic nerve),vagotomy(Vag) or adrenalectomy(Adx) were performed bilaterally in rats.Number of fecal pellet output of these rats was measured during 1-h water avoidance stress(WAS).To evaluate the colonic transit,rats were given phenol red through the catheter indwelled in the proximal colon and subjected to WAS.After WAS session,entire colon and rectum were isolated and distribution of phenol red was measured.Distal colonic and rectal transit was evaluated using glass bead.Rats were inserted the glass bead into the distal colon and evacuation rate of the bead was measured.Neural activation was assessed by immunohistochemical staining of c-Fos and PGP9.5 in colonic whole-mount preparations of longitudinal muscle myenteric plexus(LMMP).RESULTS:In the sham-operated rats(sham op),WAS significantly increased defecation and accelerated colorectal transit with marked elevation of plasma corticosterone level.Compared with sham-operated rats,increase in the excretion of fecal pellets during WAS was significantly reduced by rectal nerve transection(RNT)(sham op:6.9 ± 0.8 vs RNT:4.3 ± 0.6,P < 0.05) or Vag(sham op:6.4 ± 0.8 vs Vag:3.7 ± 1.1,P < 0.05),although corticosterone level remained elevated.Adx-rats significantly increased the defecation despite the lower corticosterone level.Distribution pattern of phenol red showed RNT inhibited distal colonic and rectal transit accelerated by WAS,while Vag inhibited proximal colonic transit.Suppression of distal colonic and rectal transit by RNT was further confirmed by the bead evacuation rate(sham op:80.0% vs RNT:53.8%).WAS significantly increased the number of c-Fos-immunoreactive neural cells in the LMMP of the proximal and distal colon,whereas c-Fos expression was decreased by RNT in the distal colon(sham op:9.0 ± 2.0 vs RNT:4.4 ± 1.0,P < 0.05) and decreased by V     

Multispecies probiotic protects gut barrier function in experimental models

AIM:To investigate the effect of the probiotic combination Lactibiane Tolerance?(LT)on epithelial barrier function in vitro and in vivo.METHODS:The effect of the multispecies probiotic LT was assessed on several models of epithelial barrier function both in vitro(in basal and inflammatory conditions)and in vivo[visceral hypersensitivity induced by chronic stress or by colonic perfusion of a fecal supernatant(FSN)from patients with irritable bowel syndrome(IBS)].In vitro,we measured the permeability of confluent T84 cell monolayers incubated with or without LT by evaluating the paracellular flux of macromolecules,in basal conditions and after stimulation with lipopolysaccharide(LPS)or with conditioned medium of colonic biopsies from IBS patients(IBS-CM).In vivo,male C57/Bl6 mice received orally NaCl or LT for 15 d and were submitted to water avoidance stress(WAS)before evaluating visceral sensitivity by measuring the myoelectrical activity of the abdominal muscle and the paracellular permeability with 51Cr-EDTA.Permeability and sensitivity were also measured after colonic instillation of FSN.Tight-junctions were assessed by immunoblotting and TLR-4 expression was evaluated by immunohistochemistry RESULTS:Incubation of T84 cell monolayers with LT in basal conditions had no significant effect on permeability(P>0.05 vs culture medium).By contrast,addition of LT bacterial bodies(LT)completely prevented the LPS-induced increase in paracellular permeability(P<0.01 vs LPS 10 ng/mL(LPS 10);P<0.01 vs LPS 100ng/mL(LPS 100),P>0.05 vs culture medium).The effect was dose dependent as addition of 109 LT bacterial bodies induced a stronger decrease in absorbance than 106 LT(109 LT+LPS 10:-20.1%±13.4,P<0.01vs LPS 10;106 LT+LPS 10:-11.6%±6.2,P<0.01 vs LPS 10;109 LT+LPS 100:-14.4%±5.5,P<0.01 vs LPS 100;106 LT+LPS 100:-11.6%±7.3,P<0.05 vs LPS 100).Moreover,the increase in paracellular permeability induced by culturing T84 cells with conditioned medium of colonic biopsies from IBS patients(IBS-CM)was completely inhibited in the presence of 109 LT(P<0.01 vs IBS-CM).LT also significantly prevented the epithelial disruption induced by intracolonic infusion of fecal supernatant from IBS patients(P<0.01 vs IBS FSN)or water avoidance stress P<0.01 vs WAS)in C57/Bl6 mice and increased the expression of occludin in vitro and in vivo,as assessed by immnunoblotting.The WAS-induced effect on visceral sensitivity was prevented by LT treatment since values obtained for all steps of colorectal distension were significantly(P<0.01)different from the WAS group.Finally,LT downregulated the response mediated through TLR-4 in vitro(decrease in tumor necrosis factorαsecretion in response to LPS:-65.8%for 109 LT and-52.5%for 106LT,P<0.01 vs LPS)and in vivo(inhibition of WAS induced an increase in TLR-4 expression in the LT treated mice colon,P<0.01 vs WAS).CONCLUSION:The probiotic LT mix prevented the disruption to the epithelial barrier induced by LPS,stress or colonic soluble factors from IBS patients and prevented visceral hypersensitivity.     

Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats

AIM:To investigate the protective effects of ethyl pyruvate(EP) on acute-on-chronic liver failure(ACLF) in rats.METHODS:An ACLF model was established in rats,and animals were randomly divided into normal,model and EP treatment groups.The rats in EP treatment group received EP(40 mg/kg) at 3 h,6 h,12 h and 24 h after induction of ACLF.Serum endotoxin,high mobility group box-1(HMGB1),alanine transaminase(ALT),tumor necrosis factor-(TNF-),interferon-(IFN-),interleukin(IL)-10 and IL-18 levels,changes of liver histology and HMGB1 expressions in liver tissues were detected at 48 h after induction of ACLF.The effects of EP on the survival of ACLF rats were also observed.RESULTS:Serum levels of endotoxin(0.394 ± 0.066 EU/mL vs 0.086 ± 0.017 EU/mL,P 0.001),HMGB1(35.42 ± 10.86 g/L vs 2.14 ± 0.27 g/L,P 0.001),ALT(8415.87 ± 3567.54 IU/L vs 38.64 ± 8.82 IU/L,P 0.001),TNF-(190.77 ± 12.34 ng/L vs 124.40 ± 4.12 ng/L,P 0.001),IFN-(715.38 ± 86.03 ng/L vs 398.66 ± 32.91 ng/L,P 0.001),IL-10(6.85 ± 0.64 ng/L vs 3.49 ± 0.24 ng/L,P 0.001) and IL-18(85.19 ± 3.49 ng/L vs 55.38 ± 1.25 ng/L,P 0.001) were significantly increased,and liver tissues presented severe pathological injury in the model group compared with the normal group.However,EP administration significantly improved hepatic histopathology and reduced the serum levels of endotoxin(0.155 ± 0.045 EU/mL vs 0.394 ± 0.066 EU/mL,P 0.001) and inflammatory cytokines(11.13 ± 2.58 g/L vs 35.42 ± 10.86 g/L for HMGB1,3512.86 ± 972.67 IU/L vs 8415.87 ± 3567.54 IU/L for ALT,128.55 ± 5.76 ng/L vs 190.77 ± 12.34 ng/L for TNF-,438.16 ± 38.10 ng/L vs 715.38 ± 86.03 ng/L for IFN-,3.55 ± 0.36 ng/L vs 6.85 ± 0.64 ng/L for IL-10,and 60.35 ± 1.63 ng/L vs 85.19 ± 3.49 ng/L for IL-18,respectively,P 0.001),and the levels of HMGB1 in liver tissues regardless of treatment time after induction of ACLF.EP treatment at the four time points prolonged the median survival time of ACLF rats(60 h) to 162 h,120 h,102 h and 78 h,respectively(2 = 41.17,P 0.0001).CONCLUSION:EP administration can protect against ACLF in rats,and is a potential and novel therapeutic agent for severe liver injury.     

Lower esophageal sphincter relaxation is impaired in older patients with dysphagia

AIM: To characterize the effects of age on the mechanisms underlying the common condition of esophageal dysphagia in older patients, using detailed manometric analysis. METHODS: A retrospective case-control audit was performed on 19 patients aged ≥ 80 years (mean age 85 ± 0.7 year) who underwent a manometric study for dysphagia (2004-2009). Data were compared with 19 younger dysphagic patients (32 ± 1.7 years). Detailed manometric analysis performed prospectively included basal lower esophageal sphincter pr...     

Can non-invasive measurements aid clinical assessment of volume in patients with cirrhosis?

AIM:To evaluate the non-invasive assessments of volume status in patients with cirrhosis.METHODS:Echocardiography and multifrequency bioimpedance analysis measurements and short synacthen tests were made in 20 stable and 25 acutely decompensated patients with cirrhosis.RESULTS:Both groups had similar clinical assessments,cortisol response and total body water(TBW),however the ratio of extracellular water(ECW)/TBW was significantly greater in the trunk(0.420±0.004 vs0.404±0.005),and limbs(R leg 0.41±0.003 vs 0.398±0.003,P<0.05,and L leg 0.412±0.003 vs 0.399±0.003)with decompensated cirrhosis compared to stable cirrhotics,P<0.05).Echocardiogram derived right atrial and ventricular filling and end diastolic pressures and presence of increased left ventricular end diastolic volume and diastolic dysfunction were similar in both groups.The decompensated group had lower systemic blood pressure,mean systolic 101.8±4.3 vs122.4±5.3 and diastolic 58.4±4.1 mmHg vs 68.8±3.1 mmHg respectively,P<0.01,and serum albumin30(27-33)vs 32(31-40.5)g/L,P<0.01.CONCLUSION:Decompensated cirrhotics had greater leg and truncal ECW expansion with lower serum albumin levels consistent with intravascular volume depletion and increased vascular permeability.     

Protective effect of glutamine on intestinal injury and bacterial community in rats exposed to hypobaric hypoxia environment

AIM:To investigate the protective effect of glutamine(Gln)on intestinal injury and the bacterial community in rats exposed to hypobaric hypoxia environment.METHODS:Sprague-Dawley rats were divided into control,hypobaric hypoxia(HH),and hypobaric hypoxia+Gln(5.0 g/kg BW·d)(HG)groups.On the first 3 d,all rats were placed in a normal environment.After the third day,the HH and HG groups were transferred into a hypobaric chamber at a simulated elevation of 7000m for 5 d.The rats in the HG group were given Gln by gavage daily for 8 d.The rats in the control and HH groups were treated with the same volume of saline.The intestinal morphology,serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),interleukin-6 (IL-6),tumor necrosis factor-α(TNF-α),interferon-gamma(IFN-γ)and diamino oxidase(DAO)were examined.We also evaluated the expression levels of occludin,toll-like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65)and myeloid differentiation factor 88(MyD88),and examined the bacterial community in caecal contents.RESULTS:Hypobaric hypoxia induced the enlargement of the heart,liver,lung and kidney,and caused spleen atrophy.Intestinal villi damage was also observed in the HH group.Supplementation with Gln significantly alleviated hypobaric-induced damage to main organs including the intestine,increased serum SOD(1.14±0.03 vs 0.88±0.04,P<0.05)and MDA(8.35±1.60,P<0.01)levels and decreased serum IL-6(1172.13±30.49 vs 1407.05±34.36,P<0.05),TNF-α(77.46±0.78 vs 123.70±3.03,P<0.001),IFN-γ(1355.42±72.80 vs 1830.16±42.07,P<0.01)and DAO(629.30±9.15 vs 524.10±13.34,P<0.001)levels.Moreover,Gln significantly increased occludin(0.72±0.05 vs 0.09±0.01,P<0.001),TLR4(0.15±0.05 vs 0.30±0.09,P<0.05),MyD88(0.32±0.08 vs 0.71±0.06,P<0.01),and NF-κB p65(0.16±0.04 vs 0.44±0.03,P<0.01)expression levels and improved the intestinal bacterial community.CONCLUSION:Gln treatment protects from intestinal injury and regulates the gut flora imbalance in hypoxia environment.These effects may be related to the TLR4/MyD88/NF-κB signaling pathway.     

Yi-Qi-Zeng-Min-Tang, a Chinese medicine, ameliorates insulin resistance in type 2 diabetic rats

AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabe...     

Effects of tetrandrine on gastric mucosa and liver in portal hypertensive rats

ＥｆｅｃｔｓｏｆｔｅｔｒａｎｄｒｉｎｅｏｎｇａｓｔｒｉｃｍｕｃｏｓａａｎｄｌｉｖｅｒｉｎｐｏｒｔａｌｈｙｐｅｒｔｅｎｓｉｖｅｒａｔｓＭＵＹｉ，ＳＨＥＮＹａｏＺｏｎｇａｎｄＣＨＵＹｉＦａｎｇＳｕｂｊｅｃｔｈｅａｄｉｎｇｓｌｉｖｅｒｇａｓｔｒｉｃｍ...     

Effects of hexahydrocurcumin in combination with 5-fluorouracil on dimethylhydrazine-induced colon cancer in rats

AIM: To investigate the effects of hexahydrocurcumin (HHC), and its combination with 5-fluorouracil (5-FU) on dimethylhydrazine (DMH)-induced colon cancer in rats.METHODS: Male Wistar rats weighing 100-120 g were used as subject models. Aberrant crypt foci (ACF), early preneoplastic lesions of colon cancer, were induced by subcutaneous injection of DHM (40 mg/kg) twice a week for two weeks. After the first DMH injection, rats were treated daily with vehicle (n = 12), curcumin (CUR) (50 mg/kg) (n = 12), HHC (50 mg/kg) orally (n = 12), and treated weekly with an intraperitoneal injection of 5-FU (50 mg/kg) (n = 12), or a combination of 5-FU plus CUR (n = 12) and HHC (n = 12) at the same dosage(s) for 16 wk. The total number of ACF and large ACF were assessed. Cyclooxygenase (COX)-1 and COX-2 expression were detected by immunohistochemistry in colon tissues. The quantitative data of both COX-1 and COX-2 expression were presented as the percentage of number of positive-stained cells to the total number of cells counted. Apoptotic cells in colon tissues were also visualized using the dUTP-biotin nick end labeling method. Apoptotic index (AI) was determined as the percentage of labeled nuclei with respect to the total number of nuclei counted.RESULTS: The total number of ACF was highest in the DMH-vehicle group (1558.20 ± 17.37), however, the number of ACF was significantly reduced by all treatments, 5-FU (1231.20 ± 25.62 vs 1558.20 ± 17.37, P < 0.001), CUR (1284.20 ± 25.47 vs 1558.20 ± 17.37, P < 0.001), HHC (1086.80 ± 53.47 vs 1558.20 ± 17.37, P < 0.001), DMH-5-FU + CUR (880.20 ± 13.67 vs 1558.20 ± 17.37, P < 0.001) and DMH-5-FU + HHC (665.80 ± 16.64 vs 1558.20 ± 17.37, P < 0.001). Interestingly, the total number of ACF in the combined treatment groups, the DMH-5-FU + CUR group (880.20 ± 13.67 vs 1231.20 ± 25.62, P < 0.001; 880.20 ± 13.67 vs 1284.20 ± 25.47, P < 0.001) and the DMH-5-FU + HHC group (665.80 ± 16.64 vs 1231.20 ± 25.62, P < 0.001; 665.80 ± 16.64 vs 1086.80 ± 53.47, P < 0.001) were significantly reduced as compared to 5-FU or each treatment alone. Large ACF were also significantly reduced in all treatment groups, 5-FU (111.00 ± 7.88 vs 262.20 ± 10.18, P < 0.001), CUR (178.00 ± 7.33 vs 262.20 ± 10.18, P < 0.001), HHC (186.60 ± 21.51 vs 262.20 ± 10.18, P < 0.001), DMH-5-FU + CUR (122.00 ± 5.94 vs 262.20 ± 10.18, P < 0.001) and DMH-5-FU + HHC (119.00 ± 17.92 vs 262.20 ± 10.18, P < 0.001) when compared to the vehicle group. Furthermore, in the DMH-5-FU + CUR and DMH-5-FU + HHC groups the formation of large ACF was significantly reduced when compared to CUR (122.00 ± 5.94 vs 178.00 ± 7.33, P < 0.005) or HHC treatment alone (119.00 ± 17.92 vs 186.60 ± 21.51, P < 0.001), however, this reduction was not statistically different to 5-FU monotherapy (122.00 ± 5.94 vs 111.00 ± 7.88, P = 0.217; 119.00 ± 17.92 vs 111.00 ± 7.88, P = 0.619, respectively). The levels of COX-1 protein after all treatments were not different from normal rats. A marked increase in the expression of COX-2 protein was observed in the DMH-vehicle group. Over-expression of COX-2 was not significantly decreased by 5-FU treatment alone (95.79 ± 1.60 vs 100 ± 0.00, P = 0.198). However, over-expression of COX-2 was significantly suppressed by CUR (77.52 ± 1.68 vs 100 ± 0.00, P < 0.001), HHC (71.33 ± 3.01 vs 100 ± 0.00, P < 0.001), 5-FU + CUR (76.25 ± 3.32 vs 100 ± 0.00, P < 0.001) and 5-FU + HHC (68.48 ± 2.24 vs 100 ± 0.00, P < 0.001) in the treated groups compared to the vehicle group. Moreover, CUR (77.52 ± 1.68 vs 95.79 ± 1.60, P < 0.001), HHC (71.33 ± 3.01 vs 95.79 ± 1.60, P < 0.001), 5-FU + CUR treatments (76.25 ± 3.32 vs 95.79 ± 1.60, P < 0.001) and 5-FU + HHC (68.48 ± 2.24 vs 95.79 ± 1.60, P < 0.001) markedly decreased COX-2 protein expression more than 5-FU alone. Furthermore, the AI in all treated groups, 5-FU (38.86 ± 4.73 vs 23.56 ± 2.12, P = 0.038), CUR (41.78 ± 6.92 vs 23.56 ± 2.12, P < 0.001), HHC (41.06 ± 4.81 vs 23.56 ± 2.12, P < 0.001), 5-FU + CUR (49.05 ± 6.75 vs 23.56 ± 2.12, P < 0.001) and 5-FU + HHC (53.69 ± 8.59 vs 23.56 ± 2.12, P < 0.001) significantly increased when compared to the DMH-vehicle group. However, the AI in the combination treatments, 5-FU + CUR (49.05 ± 6.75 vs 41.78 ± 6.92, P = 0.192; 49.05 ± 6.75 vs 38.86 ± 4.73, P = 0.771) and 5-FU + HHC (53.69 ± 8.59 vs 41.06 ± 4.81, P = 0.379; 53.69 ± 8.59 vs 38.86 ± 4.73, P = 0.245) did not reach significant levels as compared with each treatment alone and 5-FU monotherapy, respectively.CONCLUSION: The combined effects of HHC with 5-FU exhibit a synergistic inhibition by decreasing ACF formation mediated by down-regulation of COX-2 expression.     

Liver cold preservation induce lung surfactant changes and acute lung injury in rat liver transplantation

AIM:To investigate the relationship between donor liver cold preservation,lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation.METHODS:Liver transplantation models were estab-lished using male Wistar rats.Donor livers were pre-served in University of Wisconsin solution at 4 ℃ for different lengths of time.The effect of ammonium pyr-rolidinedithiocarbamate (PDTC) on ALI was also detect-ed.All samples were harvested after 3 h reperfusion.The severity of ALI was evaluated by lung weight/body weight ratio,lung histopathological score,serum nitric oxide (NO) and endothelin (ET)-1 levels,lung tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels.Lung surfactants (LSs) were determined by micellar electrokinetic capillary chromatography.RESULTS:With extended donor liver cold preservation time (CPT),lung histopathological scores,serum ET-1 levels,lung weight/body weight ratio and the level of TNF-α and IL-1β in lung were increased significantly in the 180-min group compared with the sham group (3.16 ± 0.28 vs 1.12 ± 0.21,P 0.001;343.59 ± 53.97 vs 141.53 ± 48.48,P 0.001;0.00687 ± 0.00037 vs 0.00557 ± 0.00056,P 0.001;17.5 ± 3.0 vs 1.3 ± 0.3,P 0.001;10.8 ± 2.3 vs 1.8 ± 0.4,P 0.001),but se-rum NO levels decreased remarkably (74.67 ± 10.01 vs 24.97 ± 3.18,P 0.001).The expression of lung phos-phatidylcholine (PC),phosphatidylethanolamine (PE),phosphatidylinositol (PI) and phosphatidylserine (PS) increased when CPT was 120 min,and decreased when CPT was 180 min (PC:1318.89 ± 54.79 vs 1011.18 ± 59.99,P 0.001;PE:1504.45 ± 119.96 vs 1340.80 ± 76.39,P=0.0019;PI:201.23 ± 34.82 vs 185.88 ± 17.04,P=0.2265;PS:300.43 ± 32.95 vs 286.55 ± 55.55,P=0.5054).All these ALI-associated indexes could be partially reversed by PDTC treatment.CONCLUSION:Prolonged CPT could induce or inhibit the expression of LSs at the compensation or decom-pensation stage,and some antioxidants (e.g.,PDTC) may reverse the pathological process partially.     

Protective role of hydrogen-rich water on aspirin-induced gastric mucosal damage in rats

AIM: To investigate the role of the hydrogen-rich water(HRW) in the prevention of aspirin-induced gastric mucosal injury in rats. METHODS: Forty male rats were allocated into four groups: normal control group, HRW group, aspirin group, and HRW plus aspirin group. The protective efficacy was tested by determining the gastric mucosal damage score. Malondialdehyde(MDA), superoxide dismutase(SOD), myeloperoxidase(MPO), interleukin(IL)-06 and tumor necrosis factor(TNF)-α in gastric tissues were evaluated. The serum levels of IL-1β and TNF-α were also detected. Histopathology of gastric tissues and localization of Cyclooxygenase 2(COX-2) were detected using hematoxylin and eosin staining and immunohistochemistry, respectively. RESULTS: Pretreatment with HRW obviously reduced aspirin-induced gastric damage scores(4.04 ± 0.492 vs 2.10 ± 0.437, P < 0.05). The oxidative stress levels of MDA and MPO in the gastric tissues increased significantly in the aspirin-treated group compared with the HRW group(2.43 ± 0.145 vs 1.79 ± 0.116 nmol/mg prot, P < 0.05 and 2.53 ± 0.238 vs 1.40 ± 0.208 U/g tissue, P < 0.05, respectively). HRW could obviously elevated the SOD levels in the gastric tissues(37.94 ± 8.44 vs 59.55 ± 9.02 nmol/mg prot, P < 0.05). Pretreatment with HRW significantly reduced IL-06 and TNF-α in the gastric tissues(46.65 ± 5.50 vs 32.15 ± 4.83 pg/mg, P < 0.05 and 1305.08 ± 101.23 vs 855.96 ± 93.22 pg/mg, P < 0.05), and IL-1β and TNF-α in the serum(505.38 ± 32.97 vs 343.37 ± 25.09 pg/mL, P < 0.05 and 264.53 ± 28.63 vs 114.96 ± 21.79 pg/mL, P < 0.05) compared to treatment with aspirin alone. HRW could significantly decrease the COX-2 expression in the gastric tissues(staining score: 8.4 ± 2.1 vs 2.9 ± 1.5, P < 0.05). CONCLUSION: HRW pretreatment alleviated the aspirin-induced gastric lesions by inhibiting the oxidative stress, inflammatory reaction and reducing the COX-2 in the gastric tissues.     

Correlation between changes of blood pressure with insulin resistance in type 2 diabetes mellitus with 4 weeks of pioglitazone therapy

OBJECTIVE:

To examine effects of pioglitazone (PIO) on systolic, diastolic, pulse and mean blood pressures (SBP, DBP, PP and MP, respectively) in type 2 diabetes mellitus (T2DM).

MATERIALS AND METHODS:

One hundred and six normotensive patients with T2DM with mean fasting blood glucose (FBS; 183 ± 6 mg/dl) were randomly divided into two groups. Test group was treated with 15 mg of PIO in addition to metformin 500 mg three times per day in both groups. SBP, DBP, PP and MP and fasting insulin, FBS and lipid profiles were measured before and after PIO therapy.

RESULTS:

There was a significant reduction in SBP (123 ± 2 vs. 118 ± 2 mmHg, P < 0.05), PP (41 ± 1 vs. 37 ± 1 mmHg, P < 0.05), and MP (95 ± 1 vs. 91 ± 1, P < 0.05). Clinical reduction in DBP was observed but not significant (82 ± 2 vs. 81 ± 1 mmHg, P > 0.05). There was a significant correlation between decline in SBP and DBP with respective baseline values (r = 0.76, P < 0.001 and r = 0.62, P < 0.001, respectively). Changes in PP and MP strongly correlated with baseline values (r = 0.51, P < 0.05 and r = 0.56, P < 0.05, respectively). There was a parallel reduction of FBS (183 ± 2 vs. 121 ± 3, P < 0.001) but reduction in IR or lipid profiles was not significant in test group. Changes in BP were not significant in control group ( P > 0.05).

CONCLUSION:

PIO treatment of T2DM showed early reduction of SBP and MP within first 4 weeks. Results suggest that pharmacodynamic effects of PIO mainly affect the systolic component. We hereby suggest that reduction of BP by PIO is independent from mechanisms of changes in IR and dyslipidaemia in normotensive diabetic patients.     

Effects of metoclopramide on gastrointestinal myoelectric activity in rats

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Xiaotan Tongfu granules contribute to the prevention of stress ulcers

AIM:To investigate the efficacy and potential mechanism of Xiaotan Tongfu granules(XTTF)in stress ulcers.METHODS:One hundred sixty rats were randomly divided into 4 groups(n=10)as follows:the model group(MP group),the control group(CP group),the ranitidine group(RP group)and the XTTF granule group(XP group).Rats in the MP group received no drugs,rats in the CP group received 0.2 mL of a 0.9%sodium chloride solution via oral gavage,and rats in the RP and XP groups received the same volume of ranitidine(50 mg/kg)or XTTF granule(4.9 g/kg).The cold-restraint stress model was applied to induce stress ulcers after 7 consecutive days of drug administration.Afterwards,rats were sacrificed at 0,3,6 and24 h.Gastric pH was measured by a precise pH meter;gastric emptying rate(GER)was measured by using a methylcellulose test meal;myeloperoxidase activity(MPO),macrophage migration inhibitory factor(MIF),proliferating cell nuclear antigen(PCNA),and heat shock protein 70(HSP70)were measured by immunohistochemical staining;and mucosal cell apoptosis was measured by transferase dUTP nick end labeling.RESULTS:In the cold-restraint stress model,the development of stress ulcers peaked at 3 h and basically regressed after 24 h.Gastric lesions were significantly different in the RP and XP groups at each time point.Interestingly,although this index was much lower in the RP group than in the XP group immediately following stress induction(7.00±1.10 vs 10.00±1.79,P<0.05.Concerning gastric pH,between the RP and XP groups,we detected a statistically significant difference immediately after stress induction(0 h:4.56±0.47 vs 3.34±0.28,P<0.05)but not at any of the subsequent time points.For GER,compared to the RP group,GER was remarkably elevated in the XP group because a statistically significant difference was detected(3 h:46.84±2.70 vs 61.16±5.12,P<0.05;6 h:60.96±6.71 vs 73.41±6.16,P<0.05;24 h:77.47±3.17 vs 91.31±4.34,P<0.05).With respect to MPO and MIF,comparisons between the RP and XP groups revealed statisticall     

I_κB kinase-beta inhibitor attenuates hepatic fibrosis in mice

AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice rec...     

Are gastric mucosal macrophages responsible for gastric injury in acute pancreatitis?

AIM:To investigate the protective effect of clodronatecontaining liposomes against severe acute pancreatitis(SAP)-triggered acute gastric mucosal injury(AGMI) in rats.METHODS:Clodronate- and phosphate-buffered saline(PBS)-containing liposomes were prepared by reverse-phase evaporation.The SAP rat model was established by injecting sodium taurocholate into the pancreatic subcapsular space.Sprague-Dawley rats were randomly divided into three groups:control(C),SAP plus PBS-containing liposome(P) and SAP plus clodronate-containing liposome(T).Serum tumor necrosis factor(TNF)-α levels were estimated by ELISA.Pathological changes in the gastric mucosa and pancreas were observed by hematoxylin and eosin(HE) staining.Apoptotic cells were detected by terminal deoxynucleotidyl transferase d UTP nick end labeling staining.The numbers of macrophages in the gastric mucosa were analyzed by CD68 immunohistochemical staining.RESULTS:The liposomes had a mean diameter of 150 ± 30 nm.The TNF-α levels were significantly higher in the P group than that in the C group(2 h,145.13 ± 11.50 vs 23.2 ± 2.03; 6 h,245.06 ± 12.11 vs 30.28 ± 6.07,P < 0.05),and they were significantly lower in the T group than that in the P group(2 h,93.24 ± 23.11 vs 145.13 ± 11.50; 6 h,135.18 ± 13.10 vs 245.06 ± 12.11,P < 0.05).The pathological scores of the pancreas were lower in the T group than in the P group(2 h,1.88 ± 0.83 vs 4.13 ± 0.83; 6 h,2.87 ± 0.64 vs 6.25 ± 0.88,P < 0.01).The pathological scores of the gastric mucosa were also lower in the T group than in the P group(2 h,1.12 ± 0.64 vs 2 ± 0.75; 6 h,1.58 ± 0.53 vs 3 ± 1.31,P < 0.05).In addition,increased CD68 levels were observed in the gastric mucosa of the P group compared with the C group.Clodronate-containing liposomes decreased the CD68 levels in the mucosa of the T group.The apoptotic indexes of the gastric mucosa were higher in the T group than in the P group(2 h,15.7 ± 0.92 vs 11.5 ± 1.64; 6 h,21.12 ± 1.06 vs 12.6 ± 2.44,P < 0.01).CONCLUSION:Gastric macrophages contribute to the pathogenesis of gastric injury in SAP.Clodronatecontaining liposomes have protective effects against AGMI in rats with SAP.