胰岛素样生长因子对COPD大鼠膈肌凋亡的保护作用及对肺功能的影响  

Effects of Insulin-Like Growth Factor-1 on Apoptosis of Diaphgramatic Muscle Cell and Pulmonary Function in Rats with COPD

作　　者：孙丽华[1] 欧阳晓平[1] 谷伟[1] 谭焰[1] 高景蓬[1] 

机构地区：[1]南京医科大学附属南京第一医院呼吸科,江苏南京210006

出　　处：《中国呼吸与危重监护杂志》2009年第5期441-445,共5页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：南京市科技发展计划项目(编号:200301091-4)

摘　　要：目的探讨重组的人胰岛素样生长因子1(rhIGF-1)对COPD大鼠膈肌凋亡的保护作用,并观察其对肺功能的影响。方法45只雄性Wistar大鼠随机分为对照组、模型组和干预组,每组15只。模型组和干预组大鼠置于烟雾浓度为5%的密闭熏箱内(每天30 min,共28 d),第1 d和第14 d向气管内注射脂多糖200μg。干预组大鼠同时每日皮下注射rhIGF-1(60μg/100 g)1次,持续28 d。对照组不予特殊处理。第1、14、28 d各组随机取5只大鼠处死,测定各组离体膈肌的重量、细胞凋亡率、膈肌中Fas基因及蛋白表达水平。第28 d处死前测定各组大鼠的肺功能。结果28 d后模型组和干预组大鼠分钟呼气量(VE)、最大呼气流速(PEF)、深吸气量(IC)、第0.3 s用力呼气容积(FEV0.3)及膈肌质量均较对照组下降(P<0.05)。干预组膈肌质量、IC及VE值高于模型组(P均<0.05),PEF和FEV0.3与模型组比较无显著差异(P>0.05)。第14和28 d,干预组膈肌细胞凋亡率、Fas基因及蛋白表达均低于模型组(P均<0.05),仍高于对照组(P均<0.05)。结论Fas/FasL介导的凋亡途径参与了膈肌凋亡的发生,rhIGF-1可能通过干预Fas/FasL途径减少膈肌凋亡,在一定程度上改善COPD大鼠的VE和IC值。Objective To investigate the protective effects of recombinant human insulin-like growth factor-1 （rhIGF-1） on apoptosis of diaphragm in rats with COPD and its impact on pulmonary function. Methods Forty-five male Wistar rats were randomly divided into three groups,ie, a normal control group,a model group,and an IGF-1 intervention group,with 15 rats in each group. The rats in the model group and IGF-1 group were exposed to 5% smoke （30 min perday,lasting 28 days） in a sealed box,and 200 μg lipopolysaccharide was injected intratracheally on the 1^st and 14^th day. The rats in the IGF-1 group were given rhlGF-1 （60 μg/100 g） additionally by subcutaneous injection once a day, lasting 28 days. On the 1^st, 14^th ,28^th day ,5 rats from each group were sacrificed. The weight,rate of apoptosis,Fas gene and Fas protein expression of isolated diaphragms were detected. The pulmonary function was measured on the 28th day before sacrificed. Results The mass of diaphragms, minute ventilation （ VE ）, peak expiratory flow （PEF）, inspiratory capacity （IC） ,forced expiratory volume in 0.3 second （FEV0.3 ） of the model group and IGF-1 group were all decreased compared with the control group （ P 〈 0. 05 ）. The mass of diaphragms, VE, IC of the IGF-1 group were higher than those of the model group （ P 〈 0.05 ） , and the differences of PEF and FEV0.3 were not significant （P 〉 0.05）. On the 14^th,28^th day, rate of apoptosis, Fas gene and protein expressions in the IGF-1 group were lower than those in the model group, and still higher than those in the control group （ P 〈 0. 05 ）. Conclusions Fas/FasL mediated apoptosis way is involved in the diaphragm apoptosis, rhIGF-1 may reduce the apoptosis of the diaphragm and improve the VE and IC of rats with COPD by intervening Fas/FasL pathway.

关 键 词：慢性阻塞性肺疾病 胰岛素样生长因子1 膈肌 凋亡 肺功能 FAS/FASL 

分 类 号：R563.9[医药卫生—呼吸系统]