世界中医药
文章摘要
引用本文: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.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[J].世界中医药,2013,8(07):.  
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
投稿时间:2013-06-08  
DOI:10.3969/j.issn.1673-7202.2013.06.026
中文关键词:  糖尿病肾病  MMP-9  TIMP-1  通心络  KK-Ay小鼠
English Keywords:Diabetic nephropathy  MMP-9  TIMP-1  Tongxinluo  KK-Ay mice
基金项目:国家重点基础研究发展计划课题(973计划)(编号:2012CB518602)
作者单位
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 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 
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中文摘要:
      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)、24 h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Western Blot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24 h UAER、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),24 h UAER、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。
English Summary:
      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. Results: 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 (P<0.05), 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.
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