通心络对自发性2型糖尿病KK-Ay小鼠肾功能及肾组织MMP-9、TIMP-1表达的影响  

Effects of Tongxinluo on Renal Function and MMP-9、TIMP-1 Expression of Renal Tissue in Type 2 Diabetic KK-ay Mice

作　　者：邹大威[1] 高彦彬[1] 王金羊[1] 张娜[1] 赵轩[1] 朱智耀[1] 周盛楠[1] 李骄阳[1] 马鸣飞[2] 姚静娟[1] 

机构地区：[1]首都医科大学中医药学院,北京100069 [2]北京中医药大学东方医院内分泌科,北京100078

出　　处：《世界中医药》2013年第7期782-786,共5页World Chinese Medicine

基　　金：国家重点基础研究发展计划课题(973计划)(编号:2012CB518602)

摘　　要：目的:观察通心络对自发性2型糖尿病KK-Ay小鼠肾功能及肾组织降解酶系MMP-9、TIMP-1及细胞外基质成分FN、ColⅣ表达的影响,探讨通心络防治DN的作用机制。方法:采用自发性2型糖尿病KK-Ay小鼠建立糖尿病肾病模型、随机分为模型组、通心络组、西药组各16只,设立C57BL/6J小鼠16只为空白组,予通心络及缬沙坦干预12周后,测定空腹血糖(FPG)、24h尿微量白蛋白排泄率(UAER),糖化血红蛋白(HbA1c)、血清尿素氮(BUN)、血清肌酐(SCr)含量,采用WesternBlot及Realtime-PCR方法检测基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂-1(TIMP-1)蛋白及基因表达水平,采用免疫荧光方法检测纤维连接蛋白(FN)、Ⅳ胶原(Col-Ⅳ)蛋白表达水平。结果:与空白组比较,模型组小鼠24hUAER、BUN、SCr、FPG、HbA1c均明显升高(P<0.05),肾组织TIMP-1、FN、ColⅣ表达明显升高、MMP-9表达明显降低(P<0.05);与模型组比较,经通心络及缬沙坦干预后FPG及HbA1c无明显变化(P>0.05),24hUAER、BUN、SCr显著降低,肾组织TIMP-1、FN、ColⅣ表达降低、MMP-9表达升高(P<0.05)。结论:通心络可降低自发性2型糖尿病KK-Ay小鼠尿白蛋白、保护肾功能,调控降解酶系MMP-9/TIMP-1表达抑制细胞外基质沉积是其作用机制之一。Objective： To explore effects of Tongxinluo on renal function and expression of MMP-9,TIMP-1,FN,Col-IV on diabetic nephropathy mice model,and investigate mechanism of action. Methods： Diabetic male KK-Ay mice were randomly divided into three groups： the model group（ n = 16） ,the Tongxinluo group（ n = 16） and the Western medicine group（ n = 16） . A blank group was set up by male C57BL /6J （n=16） mice. After intervention with Tongxinluo and valsartan for 12 weeks,24 h Urinary albumin excretion （ 24h UAER） ,fasting plasma glucose （FPG） ,serum creatinine （Scr） ,HbA1c,serum urea nitrogen（ BUN） were examined. Expression of MMP-9,TIMP-1 were assessed by Realtime-Pcr and Western Blot. Expression of FN,Col-IV were assessed by immunofluorescence. Re- sults： Compared with blank group,model group increased significantly for the following parameters： 24 h UAER,BUN,SCr,FPG, HbA1c,TIMP-1,FN,ColⅣ expression （ P 0. 05） ,and decreased significantly in MMP-9 expression. Compared with model group, both treatment group did not show significant changes in FPG and HbA1c （ P 0. 05） ,but had lower 24 h UAER,BUN and SCr （P0.05） ,and Tongxinluo and valsartan can down-regulate TIMP-1,FN,ColⅣ expression and up-regulate the expression of MMP-9. Conclusion： Tongxinluo can decrease 24 UAER,protect renal function and inhibit extracellular matrix through regulating MMP-9 /TIMP-1 expression.

关 键 词：糖尿病肾病 MMP-9 TIMP-1 通心络 KK-AY小鼠 

分 类 号：R575[医药卫生—消化系统]