阿托伐他汀对碘普罗胺引起的糖尿病大鼠肾小管上皮细胞凋亡的影响  

Effects of atorvastatin on iopromide-induced apoptosis of renal tubular epithelial cells in diabetic rats

作　　者：邹文博[1] 苏津自[2] 许昌声[2] 蔡文钦[2] 马雯雯[3] 陈秀平[1] 王芳兵[1] 

机构地区：[1]福建医科大学附属第一医院高血压研究所,福建福州350005 [2]福建医科大学附属第一医院心血管内科,福建福州350005 [3]华中科技大学同济医学院,湖北武汉430030

出　　处：《中国病理生理杂志》2013年第8期1393-1399,共7页Chinese Journal of Pathophysiology

基　　金：福建省自然科学基金资助项目(No.2010J01150)

摘　　要：目的:观察糖尿病大鼠造影剂急性肾损伤(CI-AKI)发病过程中肾小管上皮细胞凋亡变化,并探讨阿托伐他汀对碘普罗胺引起的糖尿病大鼠肾小管上皮细胞凋亡的影响。方法:腹腔单剂量注射链脲佐菌素(STZ)建立糖尿病大鼠模型,饲养8周后糖尿病大鼠随机分为6组:空白对照组(N组)、糖尿病对照组(DM组)、糖尿病+造影剂组(DM+CM组)、糖尿病+造影剂+5 mg·kg-1·d-1阿托伐他汀组(ATO1组)、糖尿病+造影剂+10 mg·kg-1·d-1阿托伐他汀组(ATO2组)和糖尿病+造影剂+30 mg·kg-1·d-1阿托伐他汀组(ATO3组)。注入碘普罗胺注射液24 h后收集尿标本,检测尿肌酐(UCr)以及24 h尿微量白蛋白(24 h-UAlb),记录24 h尿量并计算尿微量白蛋白排泄率(24 h-UAER)。注射碘普罗胺后48 h收集血标本,检测血清肌酐(SCr)和血尿素氮(BUN),并计算内生肌酐清除率(CCr)。处死大鼠,摘取肾脏左肾行组织病理学分析,TUNEL检测凋亡情况及免疫组织化学法检测肾髓质Bax和Bcl-2蛋白的表达,并留取右肾,采用免疫印迹技术法检测肾髓质的Bcl-2及Bax蛋白表达情况。结果:与N和DM组比较,DM+CM组注入造影剂后SCr、BUN和24 h-UAER水平明显升高(P<0.05),Ccr水平明显下降,肾小管上皮细胞的凋亡明显增加,肾髓质Bax蛋白表达升高,Bcl-2蛋白表达下降;与DM+CM组比较,ATO1、ATO2和ATO3组注入造影剂后SCr、BUN和24 h-UAER水平均有下降,CCr升高,肾小管上皮细胞的凋亡明显减少,肾髓质Bax蛋白表达下降,Bcl-2蛋白表达升高,且ATO3组的变化更为明显。结论:碘普罗胺可诱导糖尿病大鼠肾小管上皮细胞的凋亡;阿托伐他汀能改善碘普罗胺引起的糖尿病大鼠肾功能损伤,此保护作用可能与之抑制碘普罗胺诱导的肾小管上皮细胞凋亡有关,且这种保护作用有剂量依赖性。AIM： To investigate the protective effect of atorvastatin （ATO） against contrast medium （CM） -in- duced apoptosis of renal tubular epithelial cells in diabetic rats. METHODS： Streptozocin-induced diabetic Wistar rats were fed for 8 weeks and then randomly divided into 5 groups： diabetes mellitus （DM） group, DM with iopromide （ a kind of CM） treatment group （ DM ＋ CM group）, and groups of DM rats treated with ATO at 5 mgkg^-1·d^-1 （ ATO1 group）, 10 mgkg^-1·d^-1 （AT02 group） and 30 mg kg^-1·d^-1 （ATO3 group） before iopromide injection. Healthy Wistar rats served as normal controls （N group）. Urine creatinine （UCr） and 24-hour urinary albumin （24 h-UAlb） were determined 24 h after iopromide injection. Serum creatinine （SCr） and blood urea nitrogen （BUN） were detected 48 h after iopromide injection, and then creatinine clearance （ CCr ） and 24-hour urinary albumin excretion rate （24 h-UAER） were calculated.The rats were sacrificed and both kidneys were removed 48 h after iopromide injection. For the left kidney, the morphology by HE staining, the renal tubular apoptosis by TUNEL and the expression of Bax and Bcl-2 by immunohistochemistry were detected. For the right kidney, the expression of Bax and Bcl-2 was measured by Western blotting. RESULTS： Compared with N and DM groups, the levels of SCr, BUN and 24 h-UAER, as well as the expression of Bax in the renal medulla were higher, the levels of Ccr and Bel-2 expression in the renal medulla were lower and TUNEL-positive cells were more in DM ＋ CM group. Compared with DM ＋ CM group, ATO attenuated these changes, especially in ATO3 group. CONCLUSION： Iopromide could cause renal tubular apoptosis. Early application of ATO could dose-dependently attenuate the development of contrast-induced acute kidney injury, partly due to suppression of iopromide-induced renal tubular apoptosis. [

关 键 词：造影剂急性肾损伤 阿托伐他汀 糖尿病 细胞凋亡 碘普罗胺 

分 类 号：R318.16[医药卫生—生物医学工程]