Basic & Clinical Medicine ›› 2014, Vol. 34 ›› Issue (2): 216-221.

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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

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

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