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Influence Of Ulinastatin On Mucosal Barrier Injury And Expression Of Zonula Occludens-1 In Severe Acute Pancreatitis Rats

Posted on:2012-11-09Degree:MasterType:Thesis
Country:ChinaCandidate:H Q CaoFull Text:PDF
GTID:2154330335977241Subject:Surgery
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Objective To study the serum levels of tumor necrosis factor-a,diamine oxidase,the expression of Tight junction protein-1 in severe acute pancreatitis rats, the relation to intestinal mucosal barrier injury ,then investigate the changes after Ulinastatin intervention. Methods Sixty SD male rats were randomly divided into sham operation(SO) group,severe acute pancreatitis(SAP) group and ulinastatin(UTI) treatment group, each group again into 6,24h 2 time points,10 rats in each time points.SAP model was made by injecting 5% bovine sodium deoxycholate into biliary-pancreatic duct, then the rats were killed at 6 and 24 hours after the injection.Tumor necrosis factor-a,diamine oxidase and histological change in pancreas and ileum were determined, At the same time,the localization and expression of Bowel mucosa ZO-1mRNA was detected by immunohistochemistry and RT-PCR. Results The levels of serum TNF-a in SO group,SAP group,UTI treatment group were(10.83±0.96)ng/L,(181.89±4.93)ng/L,(128.23±2.40)ng/L in 6h,they were (9.89±0.14)ng/L,(198.89±4.83)ng/L,(106.79±3.30)ng/L in 24h,with significant difference(P<0.05);DAO activity were(354.79±3.67)U/L,(117.21±5.58)U/L,(282.98±9.12)U/L in 6h,they were(313.36±4.43)U/L,(91.18±1.09)U/L,(234.11±8.89)U/L in 24h, with significant difference(P<0.05);The expression of ZO-1 proteins were 10.00±1.87score,1.20±0.84 score,5.80±2.86 score in 6h,they were 8.60±2.19 score,0.80±0.84 score,2.40±1.14 score in 24h,with significant difference(P<0.05) ; The expression of ZO-1mRNA were 0.8779±0.0148,0.4660±0.0230,0.7780±0.0327 in 6h,they were 0.8300±0.0235,0.5502±0.0271,0.7040±0.0114 in 24h, with significant difference(P<0.05). Compared with SO group, the levels of serum TNF-a in SAP group was significantly increased(P<0.05) both in 6h and 24h,But the DAO activity,the expression of ZO-1 mRNA and proteins were deacreased (P<0.05).Meanwhile, the pancreas and ileum mucosa villi epithelial necrosis, blood vessel hemorrhage, inflammatory cell.Compared with SAP group,the levels of serum TNF-a decreased obviously in UTI treatment group(P<0.05),But the DAO activity,the expression of ZO-1 mRNA and proteins significantly increased (P<0.05).Meanwhile,pancreas and ileum mucosa villi epithelial necrosis, blood vessel hemorrhage, inflammatory cell ligtening obviously. Conclusion The decreased expression of ZO-1 mRNA in ileum is one of the vital causes of mucosal barrier injury in SAP, probably through the excessive release of inflammtory cytokines TNF-a and the decrease of DAO activity.Ulinastatin may can inhibit the release of TNF-a and improve plasma DAO activity,then increase the expression of ZO-1 mRNA and protect the intestinal mucosa barrier.
Keywords/Search Tags:Ulinastatin, Severe acute pancreatitis, Rat, Zonula Occludens-1, Intestinal mucosal barrier
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