自噬对庆大霉素诱导的大鼠肾损伤及修复作用的研究  

Effects of Autophagy on Gentamicin-induced Kidney Injury and Renal Repair After Injury

作　　者：孙帅军 陈叶香[1] 王新宇[1] 王曼[1] 蒋宝平[1,2] 许立[1,2] 

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]江苏省中药药效与安全性评价重点实验室,江苏南京210023

出　　处：《中药新药与临床药理》2016年第1期143-147,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：江苏省高校优势学科建设工程资助(编号:苏政办发[2014]37号)

摘　　要：目的探究自噬在庆大霉素诱导的大鼠肾损伤及修复过程中的作用。方法健康SD大鼠随机分为:生理盐水(NS)组,庆大霉素(gentamicin,GM)组和雷帕霉素(rapamycin,RAP)组。NS组大鼠腹腔注射NS,其他各组大鼠每天腹腔注射GM 100 mg·kg^(-1),同时RAP组大鼠每天灌胃RAP 1.5 mg·kg^(-1),连续7 d。分别在给药2,7,17 d后采集动物肾、血、尿液等样本。观察各组大鼠肾指数、血肌酐(serum creatinine,Scr)、尿素氮(blood urea nitrogen,Bun)、尿液中肾损伤分子1(Kidney Injury Molecule1,Kim^(-1))表达水平及不同时期微管相关蛋白1轻链3(Microtubule-associated protein 1 light chain 3,LC3)的变化情况。HE染色观察各时间点肾组织病理变化。结果与NS组比较,连续7 d给予GM后,GM组和RAP组均表现出肾指数、血Bun和Scr、尿Kim-1等水平显著升高(P<0.05,P<0.01),而在第17天时,GM组和RAP组大鼠均表现出肾指数、血Bun和Scr、尿Kim-1等不同水平的降低,且RAP组降低程度较GM组明显。在第7天时,与NS组比较,GM组LC3Ⅱ/LC3Ⅰ比值显著性降低(P<0.05),RAP组LC3Ⅱ/LC3Ⅰ比值显著性升高(P<0.01),在第17 d时,GM组和RAP组LC3Ⅱ/LC3Ⅰ比值均显著性升高(P<0.05)。HE染色表明肾损伤水平出现损伤加剧后的修复现象。结论自噬能够延缓GM诱导的肾损伤的发生,同时在肾损伤后修复过程中,自噬发挥重要的保护作用。Objective To investigate the effects of autophagy on gentamicin-induced kidney injury and renal repair after injury. Methods Healthy SD rats were randomly divided into normal control group,gentamicin（GM）group and rapamycin（RAP）group. The rats in the normal control group were given intraperitoneal injection of normal saline,and rats in other groups were given intraperitoneal injection of GM 100 mg·kg^（-1） for 7 days. RAP group was simultaneously given gastric gavage of RAP 1.5 mg·kg^（-1） for 7 days. The kidney,blood and urine were sampled after administration for 2,7 and 17 days respectively. The kidney index,serum creatinine（Scr）,blood urea nitrogen（Bun）,urine kidney injury molecule 1（Kim-1）content and microtubule-associated protein 1 light chain 3（LC3）expression level at different periods were measured by the corresponding kits. The kidney tissue pathological changes were also observed. Results After medication with GA for 7 day,kidney index,Bun,Scr and urine Kim-1 in GM group and RAP group were improved as compared with the normal control group（P〈0.05,P〈0.01）. On the 17 th experimental day,kidney index,Bun,Scr and urine Kim-1 in GM group and RAP group were decreased to various degrees,and the decrease in RAP group was more obvious. On the 7 th experimental day,the ratio of LC3Ⅱ/LC3Ⅰin GM group was decreased significantly（P〈0.05）and was increased in RAP group（P〈0.01）as compared with the normal control group. On the 17 th experimental day,the ratio was increased obviously both in GM group and RAP group（P〈0.05）.HE staining results indicated a slow recovery after kidney injury became severer. Conclusion Autophagy can delay gentamicin- induced kidney injury and promote the kidney repairing after injury.

关 键 词：自噬 肾损伤 修复 LC3 

分 类 号：R285.5[医药卫生—中药学]