蛋白酶体抑制剂PS-341在重症急性胰腺炎中的治疗作用研究  

Therapeutic Effect of PS-341 for Severe Acute Pancreatitis by Modulating the Ubiquitin-proteasome Pathway

作　　者：陈丽萍[1] 詹银楚[2] 姜仁鸦[2] 胡雅国[2] 吴善水[2] 余新春[2] 陈芳建[2] 

机构地区：[1]衢州职业技术学院医学系,浙江省衢州市324000 [2]衢州市人民医院

出　　处：《中国全科医学》2010年第9期944-946,共3页Chinese General Practice

基　　金：浙江省科技厅科研基金资助项目(2006C33077)

摘　　要：目的探讨蛋白酶体抑制剂PS-341对重症急性胰腺炎的治疗作用。方法将144只小鼠用完全随机方法分成3组:PS-341治疗组(64只):注射脂多糖前0.5h腹腔注射PS-341(0.5mg/kg)0.2ml;模型对照组(40只):注射脂多糖前0.5h腹腔注射50%二甲基亚砜(DMSO)0.2ml(0.9%氯化钠溶液稀释);空白对照组(40只):用0.9%氯化钠溶液代替雨蛙素和脂多糖,依照同样的方法腹腔注射。造模后8h将小鼠处死,用自动生化分析仪检测血清淀粉酶、C反应蛋白和乳酸脱氢酶,ELISA法检测IL-1β和IL-6;光镜下观察小鼠胰腺和肺脏的病理形态;TRNEL法检测腺泡细胞的凋亡数;EMSA法检测NF-κB活性和免疫印迹法检测I-κB水平。结果与模型对照组相比,治疗组小鼠血淀粉酶、乳酸脱氢酶、C-反应蛋白、IL-1β、IL-6明显下降(P<0.05);治疗组小鼠胰腺和肺脏的病理结果显示组织的炎细胞浸润及出血明显减少(P<0.05);治疗组凋亡的腺泡细胞数明显增加(P<0.05),I-κB降解明显减少,NF-κB活性降低(P<0.05)。结论PS-341通过抑制NF-κB活性及加强细胞凋亡对重症急性胰腺炎有一定的治疗作用。Objective To investigate the protective effect of proteasome inhibitor PS-341 on severe acute pancreatitis （SAP）.Methods Totally 144 female ICR mice were randomized into three groups：.SAP models with PS-341 treatment group （n=64）,SAP models without PS-341 treatment group （n=40）,and blank control group （n=40）.SAP was induced by seven intraperitoneal injections of 50μg/kg cerulein at hourly intervals;lipopolysaccharide at a dose of 10mg/kg was administered inraperitoneally 5 hours after the first injection of cerulean.Serum amylase,C-reactive protein （CRP）,and lactate dehydrogenase （LDH） levels were detected using standard clinical procedures and immunoglobulin （IL）-1β and IL-6 were detected with ELISA.Pancreatic biochemical assays and histological examination were also performed.Results Compared with SAP models without PS-341 treatment group,the amylase,CRP,and LDH levels and the expression of IL-1β/6 significantly decreased in PS-341 treatment group （P〈0.05,P〈0.05）.Also,PS-341 significantly inhibited NF-κB activation,while the acinar cell apoptosis was significantly enhanced（P〈0.05,P〈0.05）.Conclusion PS-341 has certain therapeutic effect on SAP by inhibiting NF-κB activation and enhancing acinar cell apoptosis in pancreas.

关 键 词：重症急性胰腺炎 蛋白酶抑制药 PS-341 核因子-ΚB 

分 类 号：R576.1[医药卫生—消化系统]