Fasudil protects against isoproterenol-induced myocardial infarction in mice via inhibiting Rho/ROCK signaling pathway

F.-T. Zhou, K. Ma

Department of Pharmacy, Dongying People’s Hospital, Dongying, China. dvahmdc@163.com

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• Cardiology

OBJECTIVE: Myocardial infarction (MI) is one of the most common diseases in cardiovascular medicine, and the risk of MI is very serious. Therefore, the purpose of this study was to explore the effect of fasudil on isoproterenol (ISO)-induced MI in mice.
MATERIALS AND METHODS: Forty C57BL/6 mice were divided into four groups, namely, control group, MI group, low dose fasudil and MI treatment group (low fasudil group), high dose fasudil, and MI treatment Group (high fasudil group). MI group and the fasudil group were injected subcutaneously with ISO (85 mg/kg) twice, and every 24 h MI was induced. Low-dose and high-dose fasudil groups were treated with 3 mg/kg/day and 10 mg/kg/day for 4 weeks before the injection of ISO. Cardiac function measured in the fourth week after ISO injection, and body weight and whole heart weight were weighed. Infarct area and thickness were analyzed by HE staining. Besides, the degree of myocardial damage was measured by detecting serum CK and LDH, and excised heart tissue was detected by Real Time-Polymerase Chain Reaction (PCR) and Western blot.
RESULTS: In MI group, the cardiac function was significantly decreased: the left ventricular short axis shortening rate (FS) and left ventricular ejection fraction (EF) were significantly decreased, the left ventricular volume was significantly increased, and the myocardial injury markers CK and LDH were significantly increased. In addition, fasudil treatment significantly relieved heart function after MI in a dose-dependent manner, reducing cardiomyocytes oxidative damage, inhibiting apoptosis.
CONCLUSIONS: Fasudil can reduce ISO-induced MI, reducing cardiomyocytes oxidative damage, inhibiting apoptosis by inhibiting the Rho/ROCK signaling pathway.

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