益气解毒活络中药对早期糖尿病肾病大鼠肾脏ERK1/2信号通路的影响及对肾脏保护作用的研究  

Study of ERK1/2 pathway related to the mechanism of Yiqi Jiedu activating method in renal protection in early stage diabetic nephropathy

作　　者：杨芳[1] 李敬林[2] 依秋霞[1] 生生 

机构地区：[1]辽宁中医药大学,沈阳110847 [2]辽宁中医药大学附属医院,沈阳110032

出　　处：《中华中医药杂志》2014年第5期1630-1634,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81173153)~~

摘　　要：目的:研究益气解毒活络中药对早期糖尿病肾病(DN)大鼠肾脏ERK1/2信号通路的影响及对肾脏保护机制。方法:采用高脂高糖喂养合并STZ腹腔注射建立DN模型,将DN大鼠按血糖随机分为模型组、西药组、预防组、高量组、低量组。干预后,检测空腹血糖(FBG)、糖化血红蛋白(HbA1c)、尿微量白蛋白(mAlb)、肌酐(SCr)、尿素氮(BUN);酶联免疫法(ELISA)检测血浆及肾脏血管紧张素Ⅱ(AngⅡ)含量;蛋白印记法(Western Blot)检测肾组织ERK1/2、p-ERK1/2、CTGF、ColⅣ蛋白表达;半定量PCR检测肾组织基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制因子-1(TIMP-1)mRNA水平。结果:模型组FBG、HbA1c、mAlb、BUN明显升高(P<0.01),Scr无明显变化,AngⅡ含量明显上升(P<0.01),p-ERK1/2、CTGF及ColⅣ蛋白表达增加(P<0.01),MMP-9 mRNA表达下降(P<0.01),TIMP-1 mRNA表达升高(P<0.01);各治疗组上述指标较模型组均明显改善(P<0.01)。结论:AngⅡ、CTGF、MMP-9、TIMP-l、ColⅣ的表达变化与细胞外基质(ECM)降解减少相关,益气解毒活络中药可能部分通过抑制AngⅡ-ERK1/2-CTGF信号通路发挥保护肾脏保护作用。Objective： To investigate the effect of compound Chinese medicine Yiqi Jiedu activating method on rats with early stage diabetic nephropathy （DN） by observing expression of extraeellular signal-regulated protein kinase ERK1/2 pathway, and to explore the renopmtective mechanism. Methods： The DN rat model was established by feeding of HG and HF diet with peritoneal injection of STZ and divided into the model group, western medicine group, prevention group, high dose group, low dose group. After treatment, FBG, HbAlc and mAlb, Scr, BUN were tested. Plasma and renal tissue angiotensin Ⅱ （AngⅡ） levels were determined by Elisa; ERKI/2, p-ERK1/2, CTGF and ColIV protein expression were determined by Western Blot analysis. MMP-9, TIMP-1 mRNA were tested by RT- PCR. Results： In the model group, the levels of FBG, HbAlc and mAlb, BUN were obviously higher （P〈0.01）, Scr showed no change; the levels of Ang Ⅱ were higher （P〈0.01）. P-ERKI/2, CTGF and ColIV levels in renal tissue increased （P〈0.01）. MMP-9 mRNA decreased（P〈0.0 l）, TIMP-1 mRNA increased（P〈0.01）. All above indexes improved obviously after treatment. Conclusion： AngⅡ, CTGF, MMP-9, TIMP-1, CollV have a relationship with the decrease of ECM, the renoprotective effects of Yiqi Jiedu activating method may be partly related to inhibit Ang Ⅱ -ERKI/2-CTGF signal pathway.

关 键 词：益气解毒活络 糖尿病肾病 血管紧张素Ⅱ 细胞外信号调节蛋白激酶 结缔组织生长因子 四型 胶原 基质金属蛋白酶-9 基质金属蛋白酶组织抑制因子-1 

分 类 号：R285.5[医药卫生—中药学]