晚期缺血预适应促进低氧诱导因子的表达,减轻肾脏缺血再灌注损伤  

Protective effect of delayed ischemic preconditioning on renal ischemia/reperfusion injury via induction of hypoxia inducible factor

作　　者：徐夏莲[1] 蒋素华[1] 许迅辉[1] 刘红[1] 丁小强[1] 

机构地区：[1]复旦大学附属中山医院肾内科,上海200032

出　　处：《中国病理生理杂志》2011年第2期320-325,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30871176;No.30971374)

摘　　要：目的:探讨晚期缺血预适应对肾脏缺血再灌注损伤的作用,以及低氧诱导因子1α(HIF-1α)在其中的作用。方法:将雄性C57/BL6N小鼠随机分为3组:假手术组(sham)、缺血再灌注组(IR)和缺血预适应组(IPC)。采用夹闭双侧肾蒂30 min后恢复灌注的方法建立肾缺血再灌注小鼠模型;缺血预适应组4 d前给予肾脏15 min预缺血。观察缺血预处理对再灌注后不同时点血肌酐(Scr)、尿素氮(BUN)、肾组织形态学和细胞凋亡的影响。采用免疫组化及Western印迹法,分析HIF-1α在肾组织的表达;采用实时定量RT-PCR法,检测血管内皮生长因子(VEGF)和葡萄糖转运子-1(Glut-1)的mRNA表达。结果:再灌注24 h后,IPC组小管间质损伤程度较IR组显著减轻,Scr、BUN水平以及小管上皮细胞凋亡明显下降。IPC组的HIF-1α核内表达显著高于IR组,且HIF-1下游靶基因VEGF和Glut-1的mRNA表达亦显著增加。结论:晚期缺血预适应能够显著改善缺血再灌注后肾脏的形态和功能,这种保护作用可能与促进低氧诱导因子高表达有关。AIM ： To investigate the effects of delayed ischemic preconditioning on renal ischemia - reperfusion injury in mice and to study the role of hypoxia inducible factor let（ HIF -lot）. METHODS： Male C57/BL6N mice were randomly divided into 3 groups ： sham operation group （ sham）, ischemia/reperfusion group （IR） and ischemic precondi- tioning group（IPC）. Thirty-minute ischemia was induced by clamping renal bilateral pedicles followed by reperfusion in IR group. Fifteen -minute pre - ischemia was performed 4 days before IR in IPC group. Serum creatinine（Scr）, blood urea nitrogen（ BUN）, kidney morphology and apoptosis were observed at different time points following reperfusion. The expression of HIF - 1 α in the renal tissues was evaluated by the methods of immunohistochemistry and Western blotting analysis. The mRNA expression of vascular endothelial growth factor（VEGF） and glucose transporter - 1 （Glut - 1 ） was detected by real - time quantitative RT - PCR. RESULTS： Compared with IR group at 24 h following reperfusion, acute tubu- lointerstitial injury was significantly relieved in IPC group. The levels of Scr and BUN, and apoptosis of tubular epithelial cells were also decreased in IPC group. Nuclear expression of HIF - 1 α was higher in IPC group than that in IR group. The mRNA expression of VEGF and Glut - 1, the target genes of HIF - 1, was also increased significantly in IPC group. CON- CLUSION： Delayed ischemic preconditioning attenuates both morphologic and functional injuries induced by renal ischemia/reperfusion. This protective effect may be related to the increased expression of hypoxia inducible factor.

关 键 词：肾 缺血预处理 缺血再灌注 低氧诱导因子 

分 类 号：R692.5[医药卫生—泌尿科学]