二甲双胍对顺铂诱导急性肾损伤大鼠的治疗作用  

Therapeutic effect of metformin on rats with cisplatininduced acute kidney injury

作　　者：全娇 江雨鹏 卢蓉 陈洋 陶立坚[2] 彭张哲[2] QUAN Jiao;JIANG Yupeng;LU Rong;CHEN Yang;TAO Lijian;PENG Zhangzhe(Department of Nutriololgy,Xiangya Hospital,Central South University,Changsha 410008;Department of Nephrology,Xiangya Hospital,Central South University,Changsha 410008,China)

机构地区：[1]中南大学湘雅医院营养科,长沙410008 [2]中南大学湘雅医院肾内科,长沙410008

出　　处：《中南大学学报（医学版）》2020年第11期1355-1360,共6页Journal of Central South University ：Medical Science

摘　　要：目的:二甲双胍对急性肾损伤(acute kidney injury,AKI)的治疗作用尚不明确,本研究采用顺铂诱导的AKI大鼠作为实验模型,给予二甲双胍药物干预,探索二甲双胍对AKI大鼠的治疗作用,并初步探索其作用机制。方法:18只雄性SD大鼠适应性喂养1周后,将其随机分为正常对照组、模型组及二甲双胍治疗组,每组6只。模型组和二甲双胍治疗组大鼠采用腹腔注射顺铂(8 mg/kg)的方法建立AKI模型。二甲双胍治疗组大鼠在造模前48 h开始给予200 mg/(kg·d)的二甲双胍灌胃,正常对照组及模型组大鼠用等体积的羧甲基纤维素钠灌胃,连续给药9 d。最后一次灌胃给药后,留取大鼠24 h尿液,检测中性粒细胞明胶酶相关载脂蛋白(neutrophil gelatinase-associated lipocalin,NGAL)水平;取大鼠血液以检测肾功能;行肾组织切片HE染色后评估肾小管损伤程度;采用TUNEL法评估肾小管上皮细胞凋亡情况。结果:与正常对照组相比,模型组血尿素、血肌酐、尿NGAL水平明显升高(均P<0.05),肾小管损伤程度评分和肾小管上皮细胞凋亡数量明显增加(均P<0.05);与模型组相比,二甲双胍治疗组血尿素、血肌酐、尿NGAL水平明显降低(均P<0.05),肾小管损伤程度评分和肾小管上皮细胞凋亡数量明显减少(均P<0.05)。结论:二甲双胍对顺铂诱导AKI大鼠有治疗作用,可能减少肾小管上皮细胞的凋亡有关。Objective:The therapeutic effect of metformin on acute kidney injury remains unclear.The purpose of this study is to observe the therapeutic effect of metformin on cisplatininduced acute renal injury in rats,and to explore the mechanisms.Methods:A total of 18 male SD rats were randomly divided into 3 groups:a normal control group,a model group,and a metformin treatment group,6 in each group.The cisplatin(8 mg/kg)was intraperitoneally injected to establish the acute kidney injury model.Metformin[200 mg/(kg·d)]was given by gavage 48 hours before the cisplatin injection and continuous administration for 9 days in a fixed time.After the last intragastric administration of the drug,the blood samples were collected for measurement of renal function indicators and 24 hours urine samples were collected for the testing of neutrophil gelatinase-associated lipocalin(NGAL).Renal tissues were dyed by HE staining to evaluate the tubular damage,and TUNEL was used to evaluate the number of apoptosis cells.Results:Serum urea nitrogen and creatinine,urinary NGAL,the degree of the renal tubular damage,and the number of apoptotic cells were increased significantly in the model group compared with the normal control group(all P<0.05).After treatment with metformin,serum urea nitrogen and creatinine,urinary NGAL,the degree of the renal tubular damage,and the number of apoptotic cells were decreased significantly(all P<0.05).Conclusion:Metformin exerts a therapeutic effect on rats with acute renal injury via reduction of apoptosis.

关 键 词：二甲双胍 急性肾损伤 顺铂 细胞凋亡 

分 类 号：R692[医药卫生—泌尿科学]