山莨菪碱预防糖尿病大鼠对比剂肾病的作用机制  

Mechanism of anisodamine on prevention from contrast induced nephropathy in diabetic rats

作　　者：宗春辉[1] 赵凯[1] 高巧营[1] 李东华[1] 戈立秀 刘晋津[1] 吴腾[1] 张一[1] 张琦 ZONG Chun-Hui;ZHAO Kai;GAO Qiao-Ying(Tianjin Nankai Hospital,Tianjin 300100,China)

机构地区：[1]天津市南开医院

出　　处：《中国老年学杂志》2019年第22期5571-5576,共6页Chinese Journal of Gerontology

基　　金：国家自然科学基金项目(81503409);天津市卫生局科技基金项目(2014KZ050)

摘　　要：目的探讨山莨菪碱预防糖尿病大鼠对比剂肾病的机制。方法SD大鼠40只,腹腔注射链脲佐菌素(60 mg/kg)建立糖尿病模型,并随机分为对照组(N组)、对比剂肾病模型组(M组)、山莨菪碱组(A组)、普罗布考组(P组,即阳性对照组)。10 w后P组大鼠给予普罗布考(500 mg/kg)灌胃,连续6 d。A组在注射对比剂泛影葡胺前及注射后的不同时间点腹腔注射山莨菪碱,共7次。24 h后,取血测血肌酐(Scr)、尿素氮(BUN),取尿检测中性粒细胞明胶酶相关脂质运载蛋白(NGAL);取左肾分别用于病理检查和检测氧化应激指标;右肾用于Western印迹检测抗凋亡蛋白和促凋亡蛋白在肾内的表达水平。结果与M组比较,A组Scr、BUN、MDA及NGAL含量均明显降低(P<0.05,P<0.01);NO、NOS含量明显升高(P<0.05,P<0.01)。按N组、M组、A组、P组的顺序,抗凋亡蛋白Bcl-2、P-AKT、p-ERK、p-mTOR、p-P70S6K表达依次明显增加,而促凋亡蛋白Bax、P-JNK、caspase-3、caspase-9表达依次明显下降。结论山莨菪碱通过抗氧化应激、抑制脂质过氧化反应、抗凋亡等途径对糖尿病大鼠对比剂肾病具有较好的保护作用。Objective To investigate the mechanism of anisodamine on prevention from contrast induced nephropathy(CIN)in diabetic rats.Methods Diabetic rat model was established by abdominal single dose injection STZ 60 mg/kg.45 SD rats were randomly divided into the control(N group),the model of CIN(M group),anisodamine(A group),probucol(P group,as positive control)groups.After 10 weeks feeding,rats in the P group received intragastric administration of probucol(500 mg/kg)for 7 days.In group A,anisodamine was injected intraperitoneally at different time points before and after injection of contrast medium,7 times.After 24 h,blood samples were taken to measure Scr,BUN,urine samples were taken to measure NGAL;the left kidney was used for pathological and oxidative stress indicators;the right kidney was used for Western blot to detect the expression levels of anti apoptotic proteins and pro apoptotic proteins.Results Compared with M group,the levels of Scr,BUN,MDA and NGAL in the treatment group were significantly decreased,whereas the levels of NO and NOS were increased.According to the sequence of N,M,A and P group,Western blot showed the expression of anti apoptosis protein Bcl-2,P-AKT,P-ERK,P-mTOR and P-P70 S6 K were increased,and the pro apoptotic protein Bax,P-JNK,caspase-3,caspase-9 expression decreased.Conclusions Anisodamine might attenuate renal injury in CIN diabetic rats and these beneficial effects are mainly mediated via anti-oxidation and anti-apoptotic effects.

关 键 词：山莨菪碱 糖尿病 对比剂肾病 

分 类 号：R587[医药卫生—内分泌]