缺氧诱导因子在大鼠肾缺血再灌注损伤中的表达和意义  

Expression of HIF-1α and Oxygen Free Radicals in Renal Ischemia-Reperfusion Injury

作　　者：王丽[1] 梅长林[2] 

机构地区：[1]武警上海总队医院肾内科,上海201103 [2]第二军医大学附属长征医院肾病研究所,上海200003

出　　处：《中国中西医结合肾病杂志》2007年第2期77-80,F0002,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：国家自然科学基金资助项目(No30330640)

摘　　要：目的:探讨缺氧诱导因子-1α(HIF-1α)和氧自由基在肾脏缺血再灌注损伤中的表达情况。方法:SD大鼠随机分为假手术组、缺血组、缺血再灌注组、RNAi阴性对照缺血组及HIF-1αRNAi预处理后的缺血组和预处理后缺血再灌注组,利用RT-PCR和westernblot技术检测各组大鼠肾脏中HIF-1α和bcl-2的表达情况。检测细胞超氧化物歧化酶(SOD)的活性和丙二醛(MDA)的含量,间接反应氧自由基的生成量。测定各组大鼠肾功能。取各组大鼠肾组织切片并做HE染色。结果:缺血组HIF-1α的表达在5组中最高(P<0.05)。与缺血组对比,缺血再灌注后HIF-1α和bcl-2的表达降低,同时氧自由基的生成增加(P<0.05),肾功能明显降低,但经HIF-1αRNAi预处理后上述指标与假手术组相比改变甚微,肾功能得到明显改善。HE染色可见缺血及再灌注组排列紊乱,胞浆萎缩,纹状缘消失,细胞间质增宽,经HIF-1αsiRNA预处理后,接近假手术组水平。结论:HIF-1α的过度表达可能导致氧自由基生成增加,肾功能受损,从而加重缺血再灌注肾脏的损伤,而HIF-1αRNAi可以减轻并改善这一状况,其机制可能与上调凋亡抑制基因有关。Objective：To investigate the expression of hypoxia inducible factor 1α（HIF1α）and oxygen free radicals in renal ischemia - reperfusion injury. Methods： The SD rats were divided randomly into three groups： sham operated group, ischemia group, ischemia - reperfusion group with or without. HIF - 1α siRNA pretreatment. We detected the expression of HIF - 1α and bel - 2 by RT-PCR and western blot,and also measured the superoxide dismutase（SOD） activity and malonaldehyde（MDA） content, which represented oxygen free radicals. Paraffin slides of kidney tissue of each group was then made for HE staining. Results：The expression of HIF- 1αin ischemia groups was the highest in the five groups （P〈0.05） ,with the decrease of expression of HIF- 1α and bcl- 2 and increase of oxygen free radicals production in ischemia - reperfusion group, decreased renal function, contrast to ischemia - reperfusion group, however, the indexes above showed no more change than those of sham operated group after HIF-1α siRNA pretreatment. Cells of ischemia - reperfusion group were arranged in disorder in HE staining with withered p1αsma, vanished brush border and widened imercellu1αr substance,but cells got simi1αr with those of sham operated group after HIF- 1α siRNA pretreatment. Conclusion ：Over expression of HIF- 1α may lead to increase of oxygen free radicals, impaired renal function and subsequent aggravation kidney injury by ischemia - reperfusion,all of which could be alleviated or improved by HIF - 1α siRNA pretreatment with the probable mechanism of upregu1αtion of anti - apoptosis genes.

关 键 词：缺氧诱导因子-1α超氧化物歧化酶丙二醛肾脏缺血再灌注 

分 类 号：R692[医药卫生—泌尿科学]