法舒地尔抑制氧化应激反应减轻2型糖尿病大鼠心肌纤维化简

 目的 探讨RhoA/ROCK通路在糖尿病大鼠心肌纤维化形成中的作用。方法 高脂饮食联合腹腔注射小剂量链脲佐菌素(STZ)建立2型糖尿病大鼠模型。实验分为对照（NC）组，糖尿病（DM）组和法舒地尔干预（DF）组（每天腹腔注射10mg/kg，分两次注射）。24周末，应用HE染色观察大鼠心脏组织形态;电子显微镜观察心肌的超微结构；Masson染色观察心肌胶原沉积情况；羟脯氨酸(HYP)检测心肌胶原含量；测定超氧化物歧化酶（SOD）活力和丙二醛（MDA）含量；免疫组化法检测一氧化氮合酶（eNOS）表达；Western blot法检测心肌中磷酸化肌球蛋白磷酸酯酶靶点亚单位1（MYPT1）表达，代表ROCK活性。 结果 糖尿病组大鼠较对照组大鼠心肌组织ROCK活性明显增强（P<0.01），MDA含量增高(P<0.01)，SOD活力降低(P<0.01)，eNOS表达明显下调(P<0.01)，心肌胶原明显增多(P<0.01)。法舒地尔干预组大鼠较糖尿病组心肌组织ROCK活性显著降低（P<0.01），MDA含量降低(P<0.05)，SOD活力增加(P<0.01)， eNOS表达上调(P<0.05)，心肌胶原明显减少(P<0.01)。结论 ROCK抑制剂法舒地尔抑制心肌组织氧化应激反应并上调eNOS表达，有效地减轻2型糖尿病大鼠心肌纤维化。

Fasudil hydrochloride hydrate ameliorates myocardial fibrosis through inhibiting oxidative stress in rats with type 2 diabetes

Objective To deternine whether the RhoA/ROCK pathway is involved in the pathogenesis of myocardial fibrosis. Methods The experimental type 2 diabetic rats were established by high fat diet combined with one-time intraperitoneal injection of low dose streptozotocin (STZ).The rats were randomly divided into three groups: normal control group， diabetic group and fasudil group (intraperitoneal injection of fasudil 10 mg per kg every day, two injections).At week 24, The cardiac histological changes were observed by hematoxylin-eosin staining, transmission electron microscopy and masson staining. The volume of collagen was evaluated by hydroxyproline (HYP). The activities of the anti-oxidant enzymes (SOD) and malondialdehyde (MDA) in cardiac tissues were estimated by using commercially available kits.The eNOS activity in cardiac tissues was assessed by immunohistochemistry staining.The level of p-MYPT1 protein expression were examined by western blot. Results Compared to the control rats, the level of p-MYPT1 and the content of MDA were significantly elevated in the hearts of the diabetic group(both P<0.01),but the activities of SOD and the expression of eNOS were significantly lower than those of the NC group rats(both P<0.01). the concentrations of collagen concentration(MCC) in myocardial tissue of the DM group were higher(P＜0.01). The fasudil group elevated the activities of SOD and the expression of eNOS (both P<0.01) but restrained the level of p-MYPT1 and the content of MDA(P<0.01,P<0.05).The concentrations of MCC were lower(P<0.01). Conclusion ROCK inhibitor fasudil, ameliorates myocardial fibrosis in diabetic rats at least in part by inhibiting oxidative stress and up-regulating eNOS expression.