wortmannin对重症急性胰腺炎大鼠的保护及治疗作用  

Protective and therapeutic effect of wortmannin on severe acute pancreatitis in rats

作　　者：蔡文科[1] 窦科峰[1] 赵青川[1] 王玉同[1] 党军强[1] 周红兵[1] 

机构地区：[1]第四军医大学西京医院肝胆外科,陕西西安710033

出　　处：《中华肝胆外科杂志》2009年第3期221-225,共5页Chinese Journal of Hepatobiliary Surgery

摘　　要：目的观察磷脂酰肌醇-3激酶（PI3K）抑制剂wortmannin对重症急性胰腺炎（SAP）大鼠的保护及治疗作用并探讨其机制。方法健康成年SD大鼠90只，随机分为对照组、对照＋wortmannin组、SAP组、SAP建模前＋wortmannin组及SAP建模后＋wortmannin组，每组18只，逆行胆胰管注射50g／I，牛磺胆酸钠制备SAP模型。检测建模后大鼠血清TNF-α水平、血清淀粉酶水平、支气管肺泡灌洗液（BALF）蛋白含量、胰腺组织髓过氧化物酶（MPO）水平；观察肺组织及胰腺组织的病理变化。结果SAP组较对照组血清TNFα水平、血清淀粉酶水平、BALF蛋白含量及胰腺组织MPO水平均显著升高（P〈0．01），SAP组胰腺、肺组织病理损伤随病情进展而逐渐加重；SAP建模前＋wortmannin组与SAP建模后＋wortmannin组较对照组各项指标均升高，但较SAP组均明显降低（P〈0．01），胰腺、肺组织病理损伤较SAP组减轻；两组数值间差异无统计学意义（P〉0．05）；对照＋wortmannin组各项指标与对照组相比差异无统计学意义（P〉0．05）。结论wortmannin对sAP大鼠有一定的保护及治疗作用，其机制可能包括抑制了胰腺腺泡细胞内PI3K的活性，从而一定程度上减轻了钙超载及早期胰蛋白酶原的激活；抑制了中性粒细胞（PMN）内PI3K信号转导通路的活化，使多种炎症细胞的活化和TNF—α等炎症因子的释放受到抑制。Objective To observe the protective and therapeutic effect of wortmannin, inhibitor of phosphatidylinositol 3-kinase （PI3K）, on severe acute pancreatitis （SAP） in rats and investigate its mechanism. Methods Ninety SD rats were randomly divided into 5 groups：control group, control＋ wortmannin group, SAP group, before SAP＋ wortmannin group and after SAP＋wortmannin group （n= 18 per group）. SAP model was induced by retrograde infusion of 50 g/L sodium taurocholate into the biliopancreatic duct of rats. Serum level of tumor necrosis factor-alpha （TNF-α）, serum level of amylase,myeloperoxidase （MPO） activity of pancreatic tissue and the protein content of bronchoalveolar lavage fluids （BALF） were evaluated. Histopathological changes of lung and pancreas were ob served. Results In SAP group, serum level of TNFα, serum level of amylase, MPO activity of pancreatic tissues and the protein content of BALF were significantly elevated （P〈0.01）. The lung and pancreas injuries were gradually aggravated with disease progression. All the indicators of before SAP ＋wortmannin group and after SAP＋wortmannin group were also elevated as compared with the control group, but still significantly decreased as compared with SAP group （p〈0.01）. There was no statistical difference between the two groups. All indicators of control＋wortmannin group and control group had no statistical difference either. Conclusion Pretreatment and treatment with wortmannin could decrease the severity of pancreatitis in rats. The mechanism may be the inhibition on the activity of PI3K in pancreatic acinar cell, thus calcium overload is decreased and the activation of trypsinogen is inhibited to certain extent. Furthermore, there is the inhibition on activation of PI3K in polymorpho nuclear neutrophils （PMN）, further on the activation of many kinds of inflammatory cells and on the release of TNF-α and other inflammatory factors.

关 键 词：胰腺炎 WORTMANNIN 中性粒细胞 磷脂酰肌醇3激酶 钙超载 胰蛋白酶原 损伤/肺 

分 类 号：R686[医药卫生—骨科学]