p38MAPK信号途径抑制剂SB203580对大鼠重症急性胰腺炎胰腺组织中TNF-α表达的调控作用

p38MAPK signal pathway inhibitor SB203580's role of regulation of TNF-α expression in the pancreatic tissue of rats with severe acute pancreatitis

目的研究p38丝裂原活化蛋白激酶(p38 MAPK)信号转导通路在大鼠重症急性胰腺炎(SAP)胰腺组织中的变化规律,探讨p38 MAPK特异性抑制剂SB203580对SAP发展和胰腺组织中TNF-α表达水平的影响。方法采用胰胆管内注射牛磺胆酸钠的方法诱导大鼠重症急性胰腺炎模型,使用SB203580抑制P38MAPK信号传导通路,通过监测大鼠血清淀粉酶(Serum amylase,AMS)和TNF-α的表达检测,观察P38MAPK抑制剂SB203580对大鼠SAP发展和TNF-α表达水平的影响。结果 SAP组TNF-α的表达明显高于对照组。胰腺组织TNF-α的表达水平随胰腺炎病情的进展而升高(P<0.05),使用p38MAPK抑制剂可以显著降低TNF-α的表达(P<0.05)。结论 SB203580可能通过抑制胰腺组织p38 MAPK信号通路进而降低TNF-α的活性,减少炎症介质的释放,达到减轻胰腺损伤,治疗急性胰腺炎的目的。

Objective Studies of p38 mitogen- activated protein kinase （p38 MAPK） signal transduction pathway in rats with severe acute pancreatitis （SAP） changes of pancreatic tissue to explore the p38 MAPK inhibitor SB203580 on SAP development and pancreatic tissue TNF- α expression levels. Methods This experimental create the model of serve acute pancreatitis in rats by injection sodium taurocholate to pancreatic duct, and use SB203580 to inhibit P38MAPK pathway. We observe the influence of P38MAPK inhibitor SB203580 in SAP rats and investigate the effect of P38MAPK on SAP pathogenesis by check the content of amylase and TNF - αin serum. Results The expression of TNF - αin SAP group was higher than control group significantly. The express of TNF - αin pancreatic tissue rises with the progress of pancreatitis disease, the expression in SAP group and inhibitor group is higher than that in control group, but the expression in inhibitor group is lower than that in SAP group at all time points （P 〈 0. 05 ）. Conclusion P38MAPK may be involved in the process of severe acute pancreatitis in rats, and SB203580 can reduce the release of inflammatory mediators, mitigate the pathological damage in severe acute pancreatitis by prevent the activation of P38MAPK pathway.