缺氧诱导因子1α参与异氟醚延迟性预处理减轻小鼠肾脏缺血再灌注损伤的研究  

ISOFLURANE PRODUCES DELAYED PRECONDITIONING AGAINST RENAL ISCHEMIA/REPERFUSION INJURY VIA HYPOXIA INDUCIBLE FACTOR 1α ACTIVATION

作　　者：程剑[1] 张蕾[1] 黄瀚[2] 马大青 刘进[1] 

机构地区：[1]四川大学华西医院麻醉科,成都610041 [2]四川大学华西第二医院麻醉科 [3]英国伦敦帝国学院医学院麻醉疼痛与危重病学科

出　　处：《中国修复重建外科杂志》2010年第4期477-481,共5页Chinese Journal of Reparative and Reconstructive Surgery

基　　金：国家自然科学基金资助项目(30828030)~~

摘　　要：目的异氟醚预处理能对大鼠肾脏发挥急性期缺血保护作用,但急性期保护作用仅能维持2～3h。探讨异氟醚延迟性预处理是否能减轻肾脏缺血再灌注损伤,以及缺氧诱导因子1α(hypoxia inducible factor1α,HIF-1α)是否参与调节该保护作用。方法取雄性C57BL/6小鼠52只,体重20～25g,随机分为4组(n=13):对照组(A组)、PBS加异氟醚预处理组(B组)、无意义小干扰RNA(small interference RNA,siRNA)加异氟醚预处理组(C组)和HIF-1αsiRNA加异氟醚预处理组(D组)。气体暴露前24h C、D组小鼠经尾静脉分别给予含有50μg无意义siRNA或HIF-1αsiRNA的无RNA酶的PBS1mL;A、B组给予等体积PBS。B、C、D组给予含1.5%异氟醚和25%O2的气体持续吸入2h,A组仅吸入含25%O2的气体2h。气体暴露后24h,采用Western blot技术检测肾脏组织中HIF-1α和促红细胞生成素(erythropoietin,EPO)蛋白的表达;制备肾缺血再灌注损伤,于再灌注后24h检测血清肌酐(serum creatinine,SCr)和血尿素氮(blood urea nitrogen,BUN)水平,并观察肾组织病理学变化。结果与A组比较,B、C组HIF-1α和EPO蛋白表达明显增加(P<0.01),SCr和BUN水平以及肾小管评分明显降低(P<0.01);D组HIF-1α蛋白表达及SCr、BUN水平较A组明显下降(P<0.01)。与B、C组比较,D组HIF-1α和EPO蛋白的表达明显下降(P<0.01),SCr和BUN水平以及肾小管评分明显增加(P<0.01),肾组织损伤明显加重。结论异氟醚延迟性预处理能明显减轻肾缺血再灌注损伤,HIF-1α参与调控异氟醚的保护作用。Objective Isoflurane has an acute preconditioning effectiveness against ischemia in kidney,but this beneficial effectiveness can only last for 2-3 hours.To investigate whether isoflurane produces delayed preconditioning against renal ischemia/reperfusion（I/R）injury,and whether this process is mediated by hypoxia inducible factor 1α （HIF-1α）.Methods A total of 52 male C57BL/6 mice were randomly assigned to 4 groups（n=13 in each group）：the control group（group A）,PBS/isoflurane treated group（group B）,scrambled small interference RNA（siRNA）/isoflurane treated group （group C）,and HIF-1αsiRNA/isoflurane treated group（group D）.In groups C and D,1 mL RNase-free PBS containing 50μg scrambled siRNA or HIF-1αsiRNA was administered via tail vein 24 hours before gas exposure,respectively.Equivalent RNasefree PBS was given in groups A and B.Then the mice in groups B,C,and D were exposed to 1.5%isoflurne and 25%O2 for 2 hours;while the mice in group A received 25%O2 for 2 hours.After 24 hours,5 mice in each group were sacrificed to assesse the expressions of HIF-1αand erythropoietin（EPO）in renal cortex by Western blot.Renal I/R injury was induced with bilateral renal pedicle occlusion for 25 minutes followed by 24 hours reperfusion on the other 8 mice.At the end of reperfusion,the serum creatinine（SCr）,the blood urea nitrogen（BUN）,and the histological grading were measured.Results The expressions of HIF-1αand EPO in groups B and C were significantly higher than those in group A（P0.01）.The concentrations of SCr and BUN in groups B and C were significantly lower than those in group A,as well as the scores of tubules（P0.01）,and the injury of kidney was ameliorated noticeably in groups B and C.The expressions of HIF-1αand the concentrations of SCr and BUN in group D were significantly lower than those in group A（P0.01）.Compared with groups B and C,the expression of HIF1αand EPO in group D decreased markedly（P0.01）,the concentrations of SCr and BUN were increased

关 键 词：异氟醚 延迟性预处理 肾脏 缺血再灌注损伤 缺氧诱导因子1Α 小鼠 

分 类 号：R692[医药卫生—泌尿科学]