中文摘要：

目的：探讨丹蛭降糖胶囊对糖尿病血糖波动模型大鼠心肌纤维化的影响及其可能机制。方法：大鼠腹腔注射链脲佐菌素建立糖尿病模型,并在此基础上通过错时给予胰岛素或葡萄糖建立糖尿病血糖波动模型。在给予丹蛭降糖胶囊治疗6 w后,测定大鼠心脏指数,ELISA法测定心肌组织血管紧张素Ⅱ（AngⅡ）、Ⅰ型和Ⅲ型胶原及转化生长因子β_1（TGF-β_1）水平,Western blot法检测心肌组织Smad3磷酸化水平和基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶组织抑制物-2（TIMP-2）蛋白水平,比色法检测心肌组织总抗氧化能力（TAC）和丙二醛（MDA）水平。结果：给予丹蛭降糖胶囊治疗6 w后,模型大鼠心脏指数和心肌组织Ⅰ、Ⅲ型胶原含量较模型组显著降低（P〈0.05或P〈0.01）,心肌组织AngⅡ、TGF-β_1及磷酸化Smad3水平也显著降低（P〈0.05或P〈0.01）;同时丹蛭降糖胶囊能显著升高模型大鼠心肌组织MMP-2蛋白表达水平,降低心肌组织TIMP-2蛋白表达水平,并显著提高心肌组织总抗氧化能力,减少脂质过氧化产物MDA含量（P〈0.05或P〈0.01）。结论：丹蛭降糖胶囊能显著抑制糖尿病血糖波动模型大鼠心肌纤维化,其机制与增强心肌组织抗氧化能力、抑制心肌局部RAS激活及TGF-β_1/Smad3信号通路活化、调控MMP-2/TIMP-2蛋白表达水平有关。

英文摘要：

Objective： To investigate the effect of Danzhi Jiangtang Capsule on myocardial fibrosis in diabetic rats with fluctuated blood glucose and the possible mechanisms implicated.Methods： Following induction of diabetes with intraperitoneal injection of streptozotocin（ STZ）,rats were administered with insulin or glucose at different time during a day to induce blood glucose fluctuation.After treatment with Danzhi Jiangtang Capsule for six weeks,rats were sacrificed and the hearts were collected for the determination of cardiac mass index.Cardiac levels of angiotensin Ⅱ（ Ang Ⅱ）,type Ⅰ and type Ⅲ collagens and transforming growth factor-β_1（ TGF-β_1） were assayed by ELISA.Levels of Smad3 phosphorylation and protein expression of matrix metalloproteinase-2（ MMP-2） and tissue inhibitor of matrix metalloproteinase-2（ TIMP-2） were determined by Western blot analysis.Total antioxidant capacity and malondialdehyde（ MDA） content in cardiac tissues were measured colorimetrically.Results： Treatment with Danzhi Jiangtang Capsule for six weeks significantly reduced cardiac mass index and cardiac levels of type Ⅰ and type Ⅲ collagens（ P〈0.05 or P〈0.01）.Levels of Ang Ⅱ,TGF-β_1and Smad_3 phosphorylation in cardiac tissues were also decreased markedly（ P〈0.05 or P〈0.01）.Supplementation with Danzhi Jiangtang Capsule resulted in an evident up-regulation of MMP-2 protein and down-regulation of TIMP-2 protein expression in cardiac tissues（ P〈0.05 or P〈0.01）.In addition,Danzhi Jiangtang Capsule significantly enhanced total antioxidant capacity in diabetic rats,while cardiac content of MDA was decreased markedly（ P〈0.05 or P〈0.01）.Conclusion： Danzhi Jiangtang Capsule significantly ameliorated myocardial fibrosis in diabetic rats with fluctuated blood glucose,which might be derived from enhancement of antioxidant capacity,suppression of RAS and TGF-β_1/ Smad3 signaling pathway and regulation of MMP-2 / TIMP-2 protein expression.