硼替佐米治疗小鼠重症急性胰腺炎  

Treatment of acute pancreatitis in mice by PS-341

作　　者：詹银楚[1] 吴善水[1] 余耀生[1] 姜仁鸦[1] 林水泉[1] 姚宏宇[1] 胡雅国[1] 

机构地区：[1]浙江衢州市人民医院肝胆外科,324000

出　　处：《中华实验外科杂志》2010年第1期26-28,I0001,共4页Chinese Journal of Experimental Surgery

基　　金：浙江省科技厅资助项目（2006C33077）

摘　　要：目的 观察硼替佐米（PS-341）对小鼠重症急性胰腺炎（SAP）的治疗作用.方法 将40只ICR雌性小鼠随机分为PS-341治疗组（注射脂多糖前0.5 h腹内注射0.5 mg/kg PS-341）、模型对照组（注射脂多糖前0.5 h腹内注射50%DMSO）、空白对照组（生理盐水制模）,采用连续7次腹内注射雨蛙素（每次间隔1 h）及脂多糖制作小鼠SAP模型.最后一次注射雨蛙素后2 h麻醉小鼠,自右颈静脉取血检测血淀粉酶（Amy）、乳酸脱氢酶（LDH）、C-反应蛋白（CRP）;光镜下观察小鼠胰腺的病理形态,测定胰腺组织中髓过氧化物酶水平（MPO）,实时荧光定量聚合酶链反应（PCR）测定胰腺组织中黏附分子（ICAM-1、P-selectin、E-selectin）的含量.结果 与模型对组比较,治疗组小鼠Amy、LDH、CRP明显下降（P〈0.05）;治疗组小鼠胰腺的病理结果显示组织的炎细胞浸润及出血明显减少,胰腺组织中MPO和黏附分子的含量明显下降,两者之间差异有统计学意义（P〈0.05）.结论 PS-341对小鼠SAP有一定的治疗作用,可望给临床上治疗SAP带来希望和前景.Objective To observe the therapeutic effects of PS-341 in the treatment of severe acute pancreatitis（SAP）in mice.Methods SAP was induced by cerulin and lipopolysaccharide（LPS）in mice.Thirty min before the administration of LPS,mice were treated with either PS-341 or vehicle.Serum amylase,C-reactive protein（CRP）,and lactate dehydrogenase（LDH）were assessed,and tissue myeloperoxidase activity was measured.The expression of intercellular adhesion molecule 1,P-selectin,E-selectin in pancreas was detected by reverse transcriptase-polymerase chain reaction （RT-PCR）.The pancreatic tissue samples were examined pathologically.Results Treatment with PS-341 significantly protected mice by attenuating myeloperoxidase activity,pancreatic morphological changes in histological sections,and down-regulating the mRNA expression of intercellular adhesion molecule 1,P-selectin,and E-selectin in pancreas as compared with vehicle-treated groups.Conclusion PS-341 may be a promising drug to prevent disease progression in SAP.

关 键 词：重症急性胰腺炎 黏附分子 蛋白酶体抑制剂 

分 类 号：R576[医药卫生—消化系统]