蛋白酶体抑制剂MG-132对慢性阻塞性肺疾病大鼠炎症因子表达的影响  

Effects of Proteasome Inhibitor MG-132 on Expression of Inflammatory Factors in COPD Rats

作　　者：马碧蔓[1] 刘朝晖[1] 梁志科[1] 关丽君[1] 汪新龙[1] 

机构地区：[1]广州医学院附属广州市第一人民医院,广东广州510180

出　　处：《中国呼吸与危重监护杂志》2013年第3期232-236,共5页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：广东省自然科学基金项目(编号:10151006001000012);广州市卫生局资助项目(编号:30504382207)

摘　　要：目的研究蛋白酶体抑制剂MG-132对慢性阻塞性肺疾病(COPD)大鼠炎症因子表达的影响及其可能的机制。方法采用反复烟熏联合气管内注入脂多糖法成功制备COPD模型后,随机分为4组:COPD非干预组(A组)、COPD+MG-132低浓度(0.05 mg.kg-1.d-1)处理组(B组)、COPD+MG-132高浓度(0.1 mg.kg-1.d-1)处理组(C组)和对照组,每组均为12只。分别于腹腔注射生理盐水或MG-132后1周和4周处死大鼠(每个时间点各组为6只),观察各组大鼠肺组织的病理学改变,酶联免疫吸附法(ELISA)检测各组大鼠血清与膈肌中的白细胞介素1β(IL-1β)、IL-6和IL-8的表达。结果 COPD模型组大鼠肺组织病理切片可见明显的肺气肿表现及炎症细胞浸润,应用MG-132后肺气肿及炎性浸润程度有所减轻。实验1周和4周A组、B组及C组大鼠血清IL-1β均高于对照组(P<0.05),B组和C组大鼠血清IL-1β均低于A组(P<0.05),C组干预4周时更明显。实验4周时在C组膈肌中IL-1β含量显著低于A组(P<0.05),血清和膈肌中IL-6含量显著低于A组(P<0.05),血清和膈肌中IL-8含量显著低于A组(P<0.05)。提示MG-132呈时间、剂量依赖性下调COPD模型组血清和膈肌的上述炎症因子的表达。结论 COPD是一种系统性炎症反应性疾病,其炎症不仅表现在肺部,蛋白酶体抑制剂MG-132可以下调炎症因子的表达来减轻COPD的全身炎症反应。Objective To investigate the influence of proteasome inhibitor MG-132 on inflammatory factors in COPD rats and its potential mechanism. Methods The COPD rat model was established by instillation of lipopolysaccharide and exposure to cigarette smoke. Then the rats were randomly divided into 4 groups（n = 12 in each group）, ie. a COPD model group, a COPD ＋ MG-132 low concentration group （0.05 mg- kg-1 . d-1）, a COPD ＋ MG-132 high concentration group （0. 1mg . kg-1 . d-1 ）,and a normal control group. The rats were injected intraperitoneally with different dose of MG-132 or normal saline. After 1 week and 4 weeks, 6 rats in each group were sarcrificed. Then the following parameters were determined including histopathological changes of lung tissue, and the concentrations of IL-1β, IL-6, IL-8 in serum and diaphragm via ELISA. Results The lung histopathological examination showed obvious emphysema and inflammatory infiltration in the COPD rats. These pathological changes were obviously ameliorated in two MG-132 treatment groups. The IL-1 β, IL-6, and IL-8 levels in serum and diaphragm in the COPD model group were all significantly increased from 1 week and 4 week than those in the normal control group（P 〈0. 05 ）. MG-132 down-regnlated the expression of these inflammatory factors in a time-and dose- dependent manner. The IL-1β, IL-6, and IL-8 levels in serum and diaphragm in the MG-132 low concentration group and high concentration group were all decreased compared with the COPD model group （P 〈 0. 05 ）. Conclusion COPD is a systemic inflammatory disease which can be inhibited by the proteasome inhibitor MG-132 through suppressing inflammatory factors.

关 键 词：慢性阻塞性肺疾病 泛素 蛋白酶体抑制剂 MG-132 炎症因子 

分 类 号：R563.9[医药卫生—呼吸系统]