miRNA-21和左旋精氨酸在大鼠肾缺血再灌注损伤中的作用  

The effect of microRNA-21 and L-arginine on renal ischemia-reperfusion injury of rat

作　　者：徐婷 马龙[2] 王毅[2] 于湘友[2] 吴昆[3] 李元媛[1] XU Ting;MA Long;WANG Yi;YU Xiangyou;WU Kun;LI Yuanyuan(Central Laboratory of Huai′an First People′s Hospital,Nanjing Medical University, Huai′an Jiangsu 223300,China;Department of Intensive Care Unit,The First Affiliated Hospital,Xinjiang Medical University,Urumqi 830054,China;Huai′an First People′s Hospital, Nanjing Medical University,Huai′an,Jiangsu 223300,China)

机构地区：[1]南京医科大学附属淮安第一医院中心实验室,江苏淮安223300 [2]新疆医科大学第一附属医院重症医学科,乌鲁木齐830000 [3]南京医科大学附属淮安第一医院,江苏淮安223300

出　　处：《新疆医科大学学报》2018年第2期203-207,共5页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区自然科学基金(2013211A090)

摘　　要：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24h和30min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。ObjectiveTo investigate the molecular regulation and function of miRNA-21 on protective effects of L-arginine(L-Arg)in renal ischemia-reperfusion injury.MethodsMice 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.ResultsL-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.ConclusionThese results indicate that miRNA-21 contributes to the renoprotective effect of L-arginine preconditioning.

关 键 词：微小RNA 急性肾损伤 肾缺血再灌注损伤 

分 类 号：R617[医药卫生—外科学]