硼替佐米对小鼠急性出血坏死性胰腺炎肺损伤的治疗作用  

Experimental Study of Bortezomib in Protecting Acute Pancreatitis-Associated Lung Injury in Mice

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

机构地区：[1]浙江省衢州市人民医院肝胆外科,衢州324000

出　　处：《中国中西医结合外科杂志》2012年第1期43-46,共4页Chinese Journal of Surgery of Integrated Traditional and Western Medicine

基　　金：浙江省科技厅资助项目(2006C33077)

摘　　要：目的:观察硼替佐米对小鼠急性出血坏死性胰腺炎肺损伤的治疗作用。方法:连续7次腹内注射雨蛙素(每次间隔1h)及脂多糖,制作小鼠重症急性胰腺炎(SAP)模型;将30只ICR雌性小鼠随机分为治疗组(注射脂多糖前0.5h腹内注射0.5mg/kg硼替佐米)、模型组(注射脂多糖前0.5h腹内注射50%DMSO)、空白组。最后一次注射雨蛙素2h后麻醉小鼠,自右颈静脉取血检测血淀粉酶、LDH、CRP;光镜下观察小鼠胰腺和肺脏的病理形态,测定肺组织中MPO水平,实时荧光定量PCR测定肺组织中黏附分子ICAM-1、E-selectin、P-selectin的含量。结果:与模型组相比,治疗组小鼠血淀粉酶、LDH、CRP明显下降(P<0.05);治疗组小鼠胰腺和肺脏炎细胞浸润及出血明显减少(P<0.05),肺组织MPO和黏附分子的含量明显下降(P<0.05)。结论:硼替佐米通过抑制黏附分子表达,减少中性粒细胞浸润,对小鼠胰腺炎肺损伤有一定的治疗作用。Objective To observe the therapeutic effect of Bortezomib（PS-341） on experimental acute pancreatitis-associated lung injury in mice.Methods Severe acute pancreatitis was induced by cerulin and lipopolysaccharide（LPS） in mice.Thirty minutes before the administration of lipopolysaccharide,the mice were treated either PS-341 or DMSO.Pancreatic inflammation and lung injury were assessed.The expression of intercellular adhension molecule 1,P-selectin,E-selectin in lung was studied by reverse transcriptase-polymerase chain reaction.Results Treatment with PS-341 significantly protected mice against pancreatitis-associated lung injury by attenuating myeloperoxidase activity,an indicator of neutrophil infiltration,lung morphological changes in histological sections,and down-regulating intercellular adhesion molecule 1,P-selectin,and E-selectin expression at mRNA in lung compared with DMSO-treated groups（P 0.05）.Conclusion PS-341 may be a promising drug to prevent disease progression in acute hemorrhagic necrotizing pancreatiits by interfering with neutrolphil infiltration.

关 键 词：急性出血坏死性胰腺炎 肺损伤 ICAM-1 选择素 硼替佐米 

分 类 号：R656.6[医药卫生—外科学] Q95-33[医药卫生—临床医学]