阿托伐他汀对2型糖尿病鼠主动脉糖基化终末产物受体基因表达的影响  

Effects of atorvastatin on expression of receptor for advanced glycation end products in aorta of type 2 diabetic rats

作　　者：冯波[1] 李栩[1] 徐雷[1] 王华[1] 颜新凤[1] 薛俊丽[1] 

机构地区：[1]同济大学附属东方医院内分泌科,上海200120

出　　处：《中华临床医师杂志（电子版）》2011年第16期4722-4725,共4页Chinese Journal of Clinicians(Electronic Edition)

基　　金：973计划项目(2006CB503900);上海市科委基础研究重点项目(08JC1419900)

摘　　要：目的观察阿托伐他汀对2型糖尿病(GK)大鼠动脉壁糖基化终末产物受体(RAGE)基因表达的影响,探讨阿托伐他汀抗糖尿病动脉粥样硬化作用的潜在机制。方法健康雄性Wistar大鼠5只作为正常对照组,GK大鼠随机分为糖尿病对照组(5只)和糖尿病阿托伐他汀治疗组(4只,每日1次阿托伐他汀20mg/kg灌胃)。各组均采用高脂饮食喂养。12周后,采用透射电镜观察主动脉壁超微结构,定量RT-PCR测定主动脉RAGE和单核细胞趋化蛋白-1(MCP-1)的表达。结果与正常对照组比较,糖尿病对照组主动脉RAGE和MCP-1表达明显升高,而阿托伐他汀治疗能够降低RAGE和MCP-1的表达。主动脉RAGE表达水平与MCP-1表达水平呈显著正相关(r=0.482,P=0.031)。透射电镜下糖尿病大鼠动脉可见超微结构的改变。结论 RAGE表达在2型糖尿病早期动脉粥样硬化形成过程中明显上调,阿托伐他汀可通过下调RAGE的表达抗动脉粥样硬化的形成。Objective To investigate the effect of atorvastatin on expression of receptor for advanced glycation end products(RAGE) in the aorta of type 2 diabetic Goto-Kakisaki(GK) rats and to discuss the potential anti-atherosclerosis mechanisms of atorvastatin.Methods 5 healthy Wistar rats(normal control group) and 9 GK rats were randomly divided into two groups:diabetic control group and atorvastatin-treated diabetic group(20 mg/kg,qd) were fed with the high fat diet for 12 weeks.The expressions of RAGE mRNA and MCP-1 mRNA of aorta were detected using RT-PCR.Ultramicrostructure of aorta was observed using electron microscope.Results Compared with normal control group,the expressions of RAGE mRNA and MCP-1 mRNA in diabetic control group were significant increased.Decreases in the expressions of RAGE mRNA and MCP-1 mRNA were observed in atorvastatin-treated diabetic group compared with diabetic control group.There was significant correlation between the expression levels of RAGE mRNA and MCP-1 mRNA(r=0.482,P=0.031).Pathomorphological changes of aorta were similar in diabetic group observed by electron microscope.Conclusions The expression of RAGE is elevated in the early stage of atherosclerosis in diabetic rats.Atorvastatin could prevent the progression of atherosclerosis partly by decreasing the expression of RAGE of aorta.

关 键 词：糖尿病 2型 动脉粥样硬化 糖基化终末产物受体 阿托伐他汀 

分 类 号：R965[医药卫生—药理学]