缺血预适应对急性缺血再灌注损伤肾小管上皮细胞自噬的影响

Effect of Ischemia Preconditioning on Epithelial Cells Autophagy of Renal Tubular in Acute Renal Ischemia Reperfusion Injury

中文关键词: 缺血预适应  肾脏  缺血再灌注  自噬  凋亡

英文关键词: ischemic preconditioning (IPC)  kidney  ischemia reperfusion  autophagy  apoptosis

中文摘要:

      目的 观察缺血预适应(ischemic preconditioning,IPC)对肾脏急性缺血再灌注(ischemia/reperfusion,I/R)损伤过程中自噬和凋亡的影响,阐明IPC对肾I/R损伤的保护作用机制.方法 雄性Sprague-Dawley大鼠随机分为3组:假手术组(Sham)、I/R组和IPC+ I/R组.分别于再灌注2、6、12和24h留取各组大鼠的血液和肾脏组织标本.采用生化分析仪检测血肌酐(Scr)水平;HE染色和原位末端标记法(TUNEL)来观察肾小管的损伤和凋亡情况;透射电镜观察肾脏自噬体结构.结果 与Sham组相比,I/R组大鼠Scr明显升高,肾组织病理损伤情况和肾细胞凋亡情况均有加重;IPC+ I/R组大鼠无论肾功能、肾组织病理损伤和细胞凋亡情况均较I/R组明显减轻.电镜结果显示,IPC+I/R组再灌注各时间点肾组织的自噬体数量均明显高于I/R组各对应时间点(P＜0.05).结论 肾脏I/R损伤过程中,自噬被诱导激活,而凋亡不断增强,IPC能够进一步活化肾小管上皮细胞自噬并抑制凋亡,从而发挥其肾保护作用.

英文摘要:

      Objective To observe the effects of ischemic preconditioning (IPC) on autophagy and apoptosis in renal acute ischemia reperfusion (I/R) injury.Methods Male Sprague-Dawley rats were randomly divided into 3 groups:Sham group,I/R group and IPC+I/R group.The specimens of blood and kidney of the rats of each group were collected at the time point of 2 hours,6 hours,12 hours and 24 hours after reperfusion.The serum creatinine (Scr) levels were measured.Tissue samples were stained with HE to observe the pathological changes.The morphology of apoptosis in kidney tissues was detected using TUNEL assay.The structures of autophagic vacuoles were observed by transmission electron microscopy (TEM).Results The Scr level of the rats in I/R group increased significantly than that of rats in sham group and renal pathological injury and cell apoptosis were both aggravated;IPC could significantly alleviate I/R injury,regardless of renal function and renal pathological tissue damage and cell apoptosis levels.TEM showed the numbers of autophagosomes were obviously higher in IPC +I/R groups at each time point after reperfusion than those of rats in I/R group at each corresponding time point (P＜0.05).Conclusion Autophagy is induced to be activated while apoptosis is enhanced in renal I/R.IPC could further activate renal tubular cell autophagy and inhibit apoptosis,thus to provide protective effect on kidney.