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

基础医学与临床 ›› 2014, Vol. 34 ›› Issue (2): 216-221.

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

李贵芝¹,周红¹,房彩霞¹,张力辉²,王绵¹,王瑞英¹

1. 河北医科大学第二医院
2. 河北医科大学第二医院内分泌科

收稿日期:2013-05-10 修回日期:2013-07-25 出版日期:2014-02-05 发布日期:2014-01-13
通讯作者: 周红 E-mail:zhoubs2013@163.com
基金资助:
2型糖尿病大鼠心肌间质重构的分子机制和法舒地尔干预

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

Received:2013-05-10 Revised:2013-07-25 Online:2014-02-05 Published:2014-01-13

摘要/Abstract

摘要： 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。

关键词: 糖尿病, 心肌纤维化, Rho激酶, 氧化应激, 法舒地尔

Abstract: 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.

Key words: diabetes, myocardial fibrosis, Rho kinase, oxidative stress, fasudil

中图分类号:

R318.11

李贵芝周红房彩霞张力辉王绵王瑞英. 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[J]. 基础医学与临床, 2014, 34(2): 216-221.

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