miRNA-21和左旋精氨酸在大鼠肾缺血再灌注损伤中的作用

摘要

Objective To investigate the molecular regulation and function of miRNA-21 on protective effects of L-arginine (L-Arg) in renal ischemia-reperfusion injury.Methods Mice were injected L-arginine through the tail vein 24 h and 30 min before the induction of renal ischemia-reperfusion injury.Levels of Serum creatinine (Scr),blood urea nitrogen (BUN) and pathological score were measured to estimate the protective effects of L-arginine on renal IRI.The role of miRNA-21,in renal protection conferred by the L-arginine preconditioning was examined by in vivo knockdown of miRNA-21 and analysis of miRNA-21 target pathways.Results L-arginine preconditioning provided protection against renal ischemia-reperfusion injury,characterized by attenuation of renal tubular damage,apoptosis,and oxidative stress.L-arginine preconditioning significantly increased the expression of miRNA-21 in the rat kidney.Mice treated with antago miRNA-21 and ischemia reperfusion injury showed significantly higher serum creatinine than antago mir-control mice,at 24 h after ischemia-reperfusion.Knockdown of miRNA-21 induced significant up-regulation of PDCD4 and PTEN,two proapoptotic target effectors of miRNA-21,and increase of tubular cell apoptosis.Conclusion These results indicate that miRNA-21 contributes to the renoprotective effect of L-arginine preconditioning.%目的 探讨左旋精氨酸(L-Arg)预处理对肾缺血再灌注损伤的保护作用及对微小RNA-21(miRNA-21)表达水平的影响,并进一步明确miRNA-21和L-Arg在肾缺血再灌注损伤作用机制.方法 大鼠缺血再灌注损伤模型构建24 h和30 min前,尾静脉注射L-Arg.通过检测血肌酐、尿素氮和病理学评分评价L-Arg对大鼠肾缺血再灌注损伤保护作用.通过antagomiRNA-21敲低体内miRNA-21后分析大鼠肾功能、组织损伤以及miRNA-21调控靶基因表达变化.结果 L-Arg预处理能改善再灌注损伤后大鼠肾功能,减轻肾组织损伤和氧化应激炎症反应,提高大鼠肾脏miRNA-21表达水平.在L-Arg预处理前敲低miRNA-21能抑制L-Arg的保护作用,加重缺血再灌注损伤,血肌酐和尿素氮水平明显升高.敲低miRNA-21导致其调控的程序性凋亡因子4(PDCD4)和PTEN表达水平明显升高.结论 L-Arg预处理使miRNA-21水平上调,对肾缺血再灌注损伤产生保护作用,其机制可能和miRNA-21调控PDCD4、PTEN有关.