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二甲双胍对2型糖尿病模型大鼠肾组织AGEs表达的影响 预览 被引量:7

Effects of metformin on expression of renal tissue AGEs in type 2 diabetic rats
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摘要 目的观察二甲双胍(MET)对2型糖尿病(T2DM)模型大鼠肾组织非酶糖基化终末产物(AGEs)及其受体(RAGE)mRNA表达的影响,探讨MET对糖尿病肾病的保护机制.方法用高脂饲料喂养结合腹腔注射小剂量链脲佐菌素(STZ)建立2型糖尿病大鼠模型.模型大鼠随机分组,给予二甲双胍干预治疗(MET组,300mg·kg^-1·d^-1)、格列本脲干预(GLY组,5mg·kg^-1· d^-1),并设立糖尿病模型组(T2DM组)和正常对照组(NC组).给药8周后,观察各组大鼠血糖(BG)、糖化血红蛋白(HbA1c)、尿素氮(BUN)、尿白蛋白和尿AGEs排泄的情况;免疫组化测肾小球AGEs蛋白表达;Real-timePCR检测肾组织RAGEmRNA表达.结果8周末,MET组及GLY组BG、HbA1c、FINS、尿白蛋白/尿肌酐(UACR)、基底膜厚度(GBMT)明显低于T2DM组,高于NC组(P〈0.05),MET组与GLY组BG、HbA1c和FINS差异无统计学意义(P〉0.05);MET组尿AGEs/尿肌酐(UGCR)、肾组织AGEs蛋白和RAGEmRNA表达明显低于糖尿病模型组(P〈0.05),但比NC组高(P〈0.05);MET组UGCR、肾组织AGEs和RAGEmRNA表达低于GLY组(P〈0.05).结论MET可减少AGEs在糖尿病大鼠肾组织的积累,并下调糖尿病大鼠肾组织RAGEmRNA的过度表达,该作用可能与其肾脏保护作用有关. Aims To observe the influences of met-formin ( MET ) on the expression of renal tissue ad-vanced glyclation end-products( AGEs) protein and its&nbsp;receptor mRNA ( RAGE mRNA ) in type 2 diabetes mellitus (T2DM) model rats, and to discuss the mech-anism of the MET in the treatment of diabetic nephrop-athy ( DN ) . Methods The rat model of T2 DM was established by fed with high-fat diet and intraperitoneal injection of low-dose of streptozotocin ( STZ ) . All rats were randomly divided into metformin group( MET,300 mg·kg-1 ·d-1 ) , glyburide group( GLY,5 mg·kg-1 ·d-1),T2DM model group(T2DM) and normal con-trol group ( NC ) . After 8 weeks ’ observation, blood glucose ( BG ) , glycated hemoglobin ( HbA1 c ) , blood urea nitrogen(BUN), urinary albumin,urinary AGEs and urine creatinine were detected. The expression of renal tissue AGEs was detected by immunohistochemis-try assay, and the expression of RAGE mRNA was measured by real-time PCR. Results The levels of BG, HbA1c , urinary albumin/urine creatinine ( UACR ) , glomerular basement membrane thickness ( GBMT ) in MET group and GLY group were signifi-cantly lower than those of T2DM group, while higher than those of NC group(P<0. 05), the levels of BG, FINS and HbA1 c were not statistically significant be-tween MET and GLY group ( P >0. 05 ) . The urinary AGEs/urine creatinine( UGCR) , the expressions of re-nal tissue AGEs and RAGE mRNA in MET group and GLY group were significantly decreased compared with those of T2 DM group ( P < 0. 05 ) , but higher than those of NC group ( P <0. 05 ) . The UGCR, the ex-pressions of AGEs and RAGE mRNA in MET group were lower than those of GLY group(P<0. 05). Con-clusion MET can reduce the accumulation of AGEs in the renal tissue,and down-regulate the over-expres-sion of RAGE mRNA in T2DM rats.
作者 李业琼 叶山东 翟丽敏 胡闻 LI Ye-qiong;YE Shan-dong;ZHAI Li-min;HU Wen;Dept of Endocrinology,Anhui Provincial Hospital Affiliated to Anhui Medical University;Dept of Pathology,Anhui Provincial Hospital Affiliated to Anhui Medical University;
出处 《中国药理学通报》 CAS CSCD 北大核心 2016年第5期703-707,共5页 Chinese Pharmacological Bulletin
基金 安徽省高校省级自然科学研究项目(NoKJ2011A157) 安徽省自然科学基金资助项目(No1508085SMH227)
关键词 2型糖尿病 糖尿病肾病 二甲双胍 AGES RAGE 格列本脲 type 2 diabetes diabetic nephropathy metformin AGEs RAGE glyburide
作者简介 李业琼(1990-),女,硕士生,研究方向:糖尿病及代谢疾病,E-mail:lyq0564@163.com 叶山东(1964-),男,博士,教授,主任医师,博士生导师,研究方向:糖尿病及代谢疾病,通讯作者,E-mail:ysd196406@163.com
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