远期缺血预适应激活热休克蛋白27、促红细胞生成素、血红素加氧酶1对肾脏缺血再灌注损伤的影响

Effect of heat shock protein 27,erythropoietin and heme oxygenase-1 activated by remote ischemic preconditioning on kidney ischemia/reperfusion injury

背景:缺血再灌注损伤是临床导致急性肾衰竭等其他疾病的重要原因,其机制为多因素、多途径的复杂的病理过程。目的:观察肾脏进行预处理后激活热休克蛋白、促红细胞生成素和血红素加氧酶1对肾脏缺血再灌注损伤的影响。方法:雄性C57BL/6小鼠90只随机分成3组。缺血再灌注组为右肾切除,左肾缺血25min再灌注24h;预适应组为双侧肾脏缺血20min再灌注8d后再进行缺血再灌注。假手术组开腹游离肾蒂。结果与结论:血清肌酐和尿素氮检测预适应组和假手术组明显低于缺血再灌注组(P<0.01);MPO染色发现缺血再灌注组大量中性粒细胞浸润(P<0.01);PAS染色发现预适应组肾组织病理情况轻于缺血再灌注组(P<0.05);TUNEL染色分析结果表明预适应组和假手术组细胞凋亡数明显少于缺血再灌注组(P<0.01);预适应组热休克蛋白27mRNA表达明显高于缺血再灌注和假手术组(P<0.05),热休克蛋白27mRNA于第8天时最强,促红细胞生成素、血红素加氧酶1mRNA在24～48h达到峰值A,然后逐渐下降,第8天后达到峰值B,B>A,并且高于假手术组(P<0.01)。提示远期缺血预适应激活热休克蛋白27、促红细胞生成素、血红素加氧酶1,能减少炎症因子浸润、促进肾小管细胞修复和抑制细胞凋亡从而参与肾脏内源性保护机制。

BACKGROUND：Ischemia-reperfusion injury is the important reasons for acute renal failure and other disease,and the mechanism is mainly the multi-factor and multi-channel complex pathological process.OBJECTIVE：To observe the influence of the heat shock protein 27（HSP27）,erythropoietin and heme oxygenase 1 activated by remote ischemic preconditioning in kidney ischemia/reperfusion injury.METHODS：Ninety male C57BL/6 mice were randomly divided into three groups：ischemia/reperfusion group（n=30）,preconditioning group（n=30）,sham operation group（n=30）.Mice in the ischemia/reperfusion group were removed the right kidney and the left kidney were subjected to ischemia for 25 minutes,and reperfusion for 24 hours;mice in the preconditioning group were subjected to bilateral renal ischemia for 20 minutes and were exposed to ischemia/reperfusion surgery on day 8 after reperfusion.Abdominal aortic blood was taken to test kidney function.RESULTS AND CONCLUSION：Serum creatinine and blood urea nitrogen of preconditioning group and the sham operation group were significantly lower than that of the ischemia reperfusion group（P 0.01）;MPO staining found a large number of neutrophils infiltration in ischemia/reperfusion group（P 0.01）;PAS staining showed that the kidney histopathology of preconditioning group was better than that of ischemia reperfusion group（P 0.05）;TUNEL staining analysis displayed that the apoptosis cells in preconditioning and sham operation group were significantly less than that in the ischemia/reperfusion group（P 0.01）;HSP27 mRNA expression in preconditioning group was significantly higher than that in the ischemia/reperfusion and sham operation group（P 0.01）,the peak of HSP27 mRNA expression was at 8 days,erythropoietin and heme oxygenase 1 mRNA were increased to A point during 24 and 48 hours,and then gradually decreased,but it was taken to another peak point B at 8 days and B was more higher than A,and the peak B in the preconditioning group was higher than that in the sham operation group（P 0.01）.Remote ischemic preconditioning activated HSP27,erythropoietin and heme oxygenase 1 mRNA expression can take part in reducing infiltration of inflammatory cytokines,promoting the repair of tubular cells and inhibiting the tubular cell apoptosis in order to protected the kidney ischemia/reperfusion injury.