大鼠重症急性胰腺炎发病机制中p38丝裂原活化蛋白激酶的作用研究

目的探讨p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)特异性抑制剂SB203580对大鼠重症急性胰腺炎(SAP)的保护作用。方法以胆胰管逆行注射5%牛磺胆酸钠建立SD大鼠SAP模型。将45只SD大鼠随机分为3组,假手术组(SO组,n=15);SAP组(SAP组,n=15);SB203580治疗组(SB组,n=15)。术后3、6、12 h处死大鼠并取血。对胰腺进行病理组织学评分,测定大鼠腹水量。检测血清淀粉酶,ELISA法测定血清IL-6和IL-10水平。并采用免疫组化法观察大鼠胰腺组织p38 MAPK下游靶点P-ATF2表达情况。结果 SO组胰腺组织存在P-ATF2弱表达,SAP组各时间点P-ATF2表达水平明显升高(P<0.01),SB组各时间点表达水平较SAP组下降明显(P<0.01)。SAP组6、12 h时间点IL-6水平,3、6 h时间点IL-10水平,血清淀粉酶,腹水量明显高于SB组(P<0.05)。SAP组各时间点胰腺组织病理学积分显著高于SB组,差异有统计学意义(P<0.05)。结论阻断p38 MAPK信号传导通路可以明显缓解大鼠重症急性胰腺炎的病情。预示此信号传导通路可以为SAP的治疗提供一个有价值的标靶。

A Research in the Protective Effect of p38 MAPK Inhibitor in SAP Rats Model

Objective To investigate the p38MAPK inhibitor SB203580 on the protective effect of severe acute pancreatitis(SAP).Methods 45 rats were randomly divided into three groups:sham operation group(SO,n=15),SAP group(SAP,n=15)and SB203580 group(SB,n=15).The model of SAP was induced by the retrograde injection of 5% sodium taurocholate(1 mg/kg) in the bile-pancreatic.Pancreatitis was evaluated by the histopathological score.Calculate lung wet/dry ratio.Serum amylase levels were measured by automatic biochemical analyzer.IL-6 and IL-10 levels were measured by enzyme-liked immunoadsordent assay(ELISA).P-ATF2 expression were determined by immunohistochemisry(IHC) staining.Results P-ATF2 expression level was a little bit low in SO group,P-ATF2 expression level at all related time points increased significartly in SAP group(P<0.05);expression level at all time points in SB group was remarkable lower than that in SAP group(P<0.05).IL-6 at 6 h and 12 h time points,IL-10 at 3 h and 6 h time points,serum amylase and ascites at all time points in SB group were lower than those in SAP(P<0.05).Pancreatitic histopathological score at all time points in SB group were lower than those in SAP significantly(P<0.05).Conclusion p38 MAPK signal transduction pathway could play a key role in the pathogenesis of SAP model.Therefore,p38 MAPK could represent a novel target for future therapies in SAP.