降糖三黄片对早期糖尿病肾病大鼠肾组织TGF-β1/Smad1信号通路的影响  

Effect of Jiangtangsanhuang Tablet on TGF-β1 /Smad1 Signal Path of Kidney Tissues of Rats with Early Diabetic Nephropathy

作　　者：江丹[1] 吴伟[2] 林明欣[3] 朱章志[4] 

机构地区：[1]广东省第二中医院,广州510095 [2]广州中医药大学,广州5104053 [3]中国中医科学院,北京100700 [4]广州中医药大学第一附属医院,广州510405

出　　处：《世界中医药》2014年第8期1067-1072,共6页World Chinese Medicine

基　　金：国家中医药管理局"十一五"重点专科课题(编号:2007BAI10B04-02)

摘　　要：目的:观察降糖三黄片对早期糖尿病肾病大鼠肾组织中转化生长因子β1(TGF-β1)、Smad1、Co1-Ⅳ的影响,探讨其对肾脏的保护作用。方法:将80只SD大鼠随机分为正常组11只、造模组69只。腹腔内注射链脲佐菌素(STZ)复制糖尿病肾病大鼠模型。造模成功的大鼠随机进一步分为模型组、厄贝沙坦组(给药量0.027 g·kg-1·d-1)、降糖三黄片组(给药量0.675 g·kg-1·d-1),给药8周后处死。于治疗前、模后4周、8周各组大鼠测血糖、称体重;造模成功后、实验结束前收集24 h尿液测定尿微量白蛋白。实验结束后摘取肾脏,去包膜称重;分别用免疫组化染色法及荧光定量RT-PCR法检测smad1、Ⅳ型胶原(Col-Ⅳ);用双抗体夹心法(ELASA)检测肾组织TGF-β1。结果:造模后各组大鼠体重明显减轻,降糖三黄片、厄贝沙坦与模型组比较,肾重/体重指数下降(P<0.01)。降糖三黄片、厄贝沙坦与模型组比较尿微量白蛋白水平下降(P<0.05)。降糖三黄片与模型组、厄贝沙坦组相比,能较好地降低血糖(P<0.01);降糖三黄片、厄贝沙坦均能明显抑制糖尿病肾病大鼠肾组织中TGF-β1的表达(P<0.01)。免疫组化染色表明厄贝沙坦组和降糖三黄片组比模型组smad1、Col-Ⅳ阳性表达程度显著减弱。免疫组化图像染色指数及荧光定量RT-PCR法结果提示降糖三黄片能降低smad1、Col-Ⅳ水平(P<0.05),且与厄贝沙坦作用相近。结论:降糖三黄片可通过抑制肾组织TGF-β1/smad1通路的表达,降低Col-Ⅳ的沉积,使肾脏的异常结构得到改善,延缓肾小球硬化。Objective：To observe the effect of Jiangtangsanhuang （JTSH）on growth factor-β1 （TGF-β1 ）,Smad1 ,Co1-Ⅳof early dia-betic nephropathy rats,and investigate its protective effect for kidney.Methods：Eighty SD rats were randomly divided into normal control group （n=11）and diabetic model group （n=69）.The diabetic models were induced by lower-dosage of streptozocin （STZ）（30mg/kg）.The model group was then divided into three sub-groups including early DN group,Irbesartan group （0.027 g·kg-1 ·d-1 ）and JTSH group（0.675 g·kg-1 ·d-1 ）.The course of treatment lasted for 8 weeks.Rats were tested with blood glucose and weighed before dosing,4 and 8 weeks after dosing.Microalbuminuria was tested after DN model was established and before execution.Weight of all rats were measured before being executed.Immunohistochemical staining and fluorescence quota RT-PCR were used to determine smad1 and Col-Ⅳ.ELASA was used to determine TGF-β1 .Results：All the rats had weight loss after being made into disease models,and JTSH and Irbesartan groups had better effect of alleviating weight/kidney weight index （P〈0.01）and 24 hours urine immunohistochemical（P〈0.05）compare to early DN group.JTSH Tablet had better effect in reducing blood glucose than Irbesartan and early DN groups（P〈0.01）.JTSH and Irbesartan groups could significantly reduce TGF-β1（P〈0.01）in rats kidney.The expression of smad1 and Col-Ⅳa-mong DN group was significantly higher than normal group by using immunohistochemical method,but there was substantial reduction in JTSH and Irbesartan groups（P〈0.01）.As dye index and fluorescence quota RT-PCR results,JTSH groups could reduce gene expression of smad1 and Col-Ⅳas well as Irbesartan.Conclusion：JTSH tablet has restrained TGF-β1/smad1 channel to deduce Col-Ⅳin kidney, so as to delay renal glomerulus sclerosis.

关 键 词：糖尿病肾病 降糖三黄片 转化生长因子-β1 Smad1通路 Col—Ⅳ 

分 类 号：R587.2[医药卫生—内分泌]