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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 Chinese herbal for invigorating qi to detoxification on the renal ERK1 / 2 signal pathway in the early stage of diabetic nephropathy (DN) rats and its protective mechanism to the kidney. Methods: DN model was established by intraperitoneal injection of high fat and high glucose and STZ. DN rats were randomly divided into model group, western medicine group, prophylaxis group, high dose group and low dose group by blood glucose. After intervention, FBG, HbA1c, mAlb, SCr and BUN were measured. Plasma and renal angiotensin Ⅱ levels were detected by enzyme-linked immunosorbent assay (ELISA) (AngⅡ). The protein expressions of ERK1 / 2, p-ERK1 / 2, CTGF and ColⅣ in renal tissues were detected by Western Blot. The expressions of MMP-9, Protease inhibitor of tissue factor 1 (TIMP-1) mRNA levels. Results: The levels of FBG, HbA1c, mAlb and BUN in model group were significantly increased (P <0.01), Scr had no significant change, Ang Ⅱ content increased significantly (P <0.01) 0.01). The mRNA expression of MMP-9 decreased (P <0.01) and the expression of TIMP-1 mRNA increased (P <0.01). Compared with the model group, the above indexes were significantly improved in all treatment groups (P <0.01). Conclusion: The expression changes of AngⅡ, CTGF, MMP-9, TIMP-1 and ColⅣ are related to the decrease of extracellular matrix (ECM) degradation. Chinese herbs of Yiqi Jiedu active may partly protect the kidneys by inhibiting the signaling pathway of AngⅡ-ERK1 / 2-CTGF Protective effects.