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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CNI1493对SAP 的保护作用. 方法:50 g/L牛磺胆酸钠胰胆管逆行注射建立雄性SD 大鼠SAP模型,随机分为SO组(假手术组,n=30)、SAP—NS组(n=25)及SAP—CNI1493组(n=25),各组大鼠质量相似.Western blot法检测大鼠胰腺组织磷酸化p38 MAPK的表达;ELISA方法检测血清IL-1β,TNF-α水平:光镜下评估胰腺组织病理学积分. 结果:SO组胰腺组织存在磷酸化p38 MAPK弱表达, SAP—NS组造模后15 min时磷酸化p38 MAPK的表达即显著增高至峰值,3 h后开始下降,6 h时磷酸化p38 MAPK活性与SO组相似.SAP—NS组和SAP-CNI1493 组Western blot检测15,30 min条带光密度值5 200±360, 3 500±250和4 910±320,2 500±340,SAP—CNI1493组15,30 min时胰腺组织磷酸化p38 MAPK的表达显著低于SAP—NS组(P<0.01).SAP-CNI1493组3,6 h时间点血清IL-1β,TNF-α水平及3 h时间点胰腺组织病理学积分均显著低于SAP—NS组(P<0.01). 结论:p38 MAPK信号转导通路与牛磺胆酸钠大鼠SAP 发病机制有关,CNI1493预处理可能通过抑制p38 MAPK的激活、减少炎症细胞因子的产生而改善腓炎病理改变的严重程度.
Objective: To study the changes of p38 mitogen-activated protein kinase (p38 MAPK) signal transduction pathway in the pancreas of severe acute pancreatitis (SAP) in rats and to explore the protective effect of p38 MAPK specific inhibitor CNI1493 on SAP.Methods : A SAP model of male SD rats was established by retrograde injection of 50 g / L sodium taurocholate into the pancreaticobiliary ducts of rats. The SAP model was randomly divided into three groups: SAP group (n = 30), SAP group (n = 25) and SAP-CNI1493 (N = 25) .The rats in each group were of similar quality.Western blot was used to detect the expression of phospho-p38 MAPK in rat pancreatic tissue.Serum levels of IL-1β and TNF-α were detected by ELISA. Results: The phosphorylation of p38 MAPK was weakly expressed in pancreatic tissue of SO group, the expression of phospho-p38 MAPK increased significantly to peak value in SAP-NS group at 15 min, and began to decrease after 3 h. At 6 h, the phosphorylation of p38 MAPK MAPK activity was similar to that in SO group.Western blot detected SSP-NS group and SAP-CNI1493 group at 15 and 30 min with optical density values of 5 200 ± 360, 3 500 ± 250 and 4 910 ± 320 and 2 500 ± 340, SAP- The expression of phosphorylated p38 MAPK in pancreas was significantly lower in CNI1493 group than that in SAP-NS group at 15 and 30 min (P <0.01). The levels of IL-1β (P <0.01) .Conclusion: The p38 MAPK signal transduction pathway is related to the pathogenesis of SAP in rats with taurocholic acid, and the level of TNF-α and the histopathological score of pancreatic tissue at 3 h are significantly lower than those in SAP- CNI1493 preconditioning may improve the severity of the pathological change of the phlebitis by inhibiting the activation of p38 MAPK and reducing the production of inflammatory cytokines.