Wy14643联合Troglitazone对急性肺损伤大鼠肺组织PPAR-α表达的影响  

Effects of Wy14643 and Troglitazone on the expression of peroxisome proliferation activated receptor-α in lung of rats with acute lung injury

作　　者：方芳[1] 王建春[1] 徐剑铖[1] 钱桂生[1] 

机构地区：[1]解放军第三军医大学新桥医院全军呼吸内科研究所,重庆400037

出　　处：《中国急救医学》2008年第7期610-613,675,共5页Chinese Journal of Critical Care Medicine

基　　金：国家自然科学基金资助(No.30570808)

摘　　要：目的探讨Wy14643联合Troglitazone作用于急性肺损伤大鼠肺组织后PPAR-α表达的变化及其意义。方法将96只大鼠随机分为对照组(ND组)、脂多糖(LPS)致伤组(LD组)、Wy14643处理组(LW组)、Wy14643联合Troglitazone处理组(LWT组)。用LPS 5 mg/kg静脉注射复制大鼠ALI模型。静脉注射Wy14643 3mg/kg(LW组)或顺序注入Wy14643 3mg/kg及Troglita-zone 3mg/kg(LWT组),30min后静脉注射LPS(注射LPS完毕后开始计时)。分别在1、2、4及8h时处死大鼠,测定用药前后各时相点大鼠肺组织湿/干质量比(W/D);观察肺组织病理变化;采用逆转录聚合酶链反应(RT-PCR)检测各时相点肺组织中PPAR-αmRNA的表达;采用免疫组织化学染色法检测各时相点肺组织中PPAR-α蛋白的表达。结果LD组大鼠肺组织干湿质量比值(W/D值)较ND组明显升高(P<0.05);LW组、LWT组的W/D比值均较LD组明显降低(P<0.05),LWT组和LW组比较差异无统计学意义(P>0.05)。结果显示,正常肺组织有PPAR-α表达,为棕黄色粗颗粒,主要表达在肺泡上皮细胞核内,胞浆未表达或有少许表达;LD组较ND组PPAR-α表达减弱(P<0.05);LW组和LWT组PPAR-α表达较LD组增强(P<0.05);LW组与LWT组比较无显著差别。结论LPS引起急性肺损伤大鼠肺组织PPAR-α表达下降,Wy14643使PPAR-α表达增强,Wy14643联合Troglitazone同样使PPAR-α表达增强,但与单用Wy14643比较无差别。Obiective To investigate effects on the expression of peroxisome proliferation activated receptor-α by Wy14643 and Troglitazone in lung of rats with acute lung injury induced by lipopolysaccharide, we want to expose the role and significance of PPAR -α in acute lung injury. Methods 96 male Wistar rats were divided randomly into four groups, ie, control group, acute lung injury group, Wy14643 group,Wy14643 ＋ Troglitazone group. The latter three groups Wistar rats were all injected in LPS（5 mg/kg} by vein,which would be provided at the end of 30 minute after vein administration with Wy14643 in LW group or Wy14643 and Troglitazone （ interval 30 min ） especially in LWT group. All rats were killed at 1,2,4,8 h after LPS challenge. Lung tissue wet/dry weight ratio, lung histopathological change were observed, expression of PPAR - α were explored by RT - PCR, proteie expression of PPAR - α by immunohistoehemistry staining method. Results Lung W/D ratio in LD group rised compare with control group （ P 〈 0.05 ） , which in LW group and LWT group decreased compare with LD group （ P 〈 0. 05） ,and those PPAR - α expression in LD group decreased compare with ND group（ P 〈0.05 ） , PPAR-α expression in LWT group and in LW group increased markedly compare with LD group （P 〈0.05）,but that in LWT group had no distinction compare with LW group （ P 〉 0.05 ）. Conclusion LPS caused decrease of PPAR - α expression in acute lung injury. Wy14643/Wy14643 ＋ Troglitazone both maked PPAR - α expression increased markedly compare with LD group, but this change in LWT group had no distinction compare with LW group.

关 键 词：过氧化物酶增殖体激活受体-α(PPAR-α) 急性肺损伤(ALI) 脂多糖 

分 类 号：R563.8[医药卫生—呼吸系统]