PS-341对小鼠重症急性胰腺炎核因子-κB活化的影响  

The effect of PS-341 on nulear factor- κB activation in mice with severe acute pancreatitis

作　　者：姜仁鸦[1] 詹银楚[1] 吴善水[1] 胡雅国[1] 董鑫[2] 

机构地区：[1]衢州市人民医院肝胆外科,浙江衢州324000 [2]浙江大学第二附属医院普外科,浙江杭州310014

出　　处：《肝胆胰外科杂志》2012年第3期232-235,共4页Journal of Hepatopancreatobiliary Surgery

基　　金：浙江省科技厅科研基金(2006C33077)

摘　　要：目的观察PS-341对重症急性胰腺炎(SAP)小鼠胰腺组织核因子-κB(NF-κB)活化的影响,阐明PS-341对SAP的作用机制。方法采用连续7次腹内注射雨蛙素(每次间隔1h)及脂多糖制作小鼠SAP模型,将60只ICR雌性小鼠随机分为PS-341治疗组(注射脂多糖前0.5h腹内注射0.5mg/kgPS-341),模型对照组(注射脂多糖前0.5h腹内注射50%DMSO),空白对照组(生理盐水制模)。最后一次注射雨蛙素后2h麻醉小鼠,取血检测血淀粉酶,光镜下观察小鼠胰腺和肺脏的病理形态,测定胰腺组织中髓过氧化物酶水平,实时荧光定量PCR测定胰腺组织中黏附分子(ICAM-1)的含量,免疫印迹法(Westernblotting)检测胰腺组织中IκBα的表达,电泳迁移率实验(EMSA)测定NF-κB活性。结果 PS-341治疗组和模型对照组比较,胰腺组织中I-κB降解减少,NF-κB活性显著下降,血清淀粉酶、MPO、胰腺组织中细胞黏附分子ICAM-1的表达都明显降低(P<0.05)。胰腺和肺脏组织病理学有明显的改善(P<0.05)。结论 PS-341通过抑制胰腺内NF-κB活化而抑制炎症反应。PS-341可能是治疗SAP的一个新措施。Obiective To observe the effect of PS-341 on nuclear factor- κ B（NF- κ B） activation in mice withsevere acute pancreatitis（SAP）. Methods SAP model was induced by cerulin and lipopolysaccharide （LPS） in mice. 30 minutes before the administration of lipopolysaccharide, mice were treated either PS-341 or vehicle. Blood samples were collected for the serum amylase. Pancreatic inflammation and lung iniurywere assessed. The expression of intercellular adhesion molecule 1 in pancreas was studied by reverse transcriptase-polymerase chain reaction. Pancreatic expression of I κ B α was measured by Western blotting analysis and the activation of NF-κ B was assessed by electrophoretic mobility shift assay. Results Compared with SAP groups, treatment with PS-341 decreased the degradation of I κ B a and inhibited NF- κ B activation with down-regulating serum amylase, myeloperoxidase activity and intercellular adhesion molecule 1. In addition, pancreatic and lung morphological changes in histological sections were markedly improved. Conclusion PS-341 may be helpful to prevent disease progression in severe acute pancreatitis by inhibition of NF- κ B activation.

关 键 词：重症急性胰腺炎 ICAM-1 蛋白酶体抑制剂 核因子-κB 小鼠 

分 类 号：R576[医药卫生—消化系统]