Department of Pharmacy, Dongying People's Hospital, Dongying, China.
Eur Rev Med Pharmacol Sci. 2020 May;24(10):5659-5667. doi: 10.26355/eurrev_202005_21357.
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.
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.
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.
Fasudil can reduce ISO-induced MI, reducing cardiomyocytes oxidative damage, inhibiting apoptosis by inhibiting the Rho/ROCK signaling pathway.
心肌梗死（MI）是心血管医学中最常见的疾病之一，MI 的风险非常严重。因此，本研究旨在探讨法舒地尔对异丙肾上腺素（ISO）诱导的小鼠 MI 的影响。
将 40 只 C57BL/6 小鼠分为 4 组，即对照组、MI 组、低剂量法舒地尔和 MI 治疗组（低法舒地尔组）、高剂量法舒地尔和 MI 治疗组（高法舒地尔组）。MI 组和法舒地尔组皮下注射 ISO（85mg/kg）两次，每 24 小时诱导 MI。低剂量和高剂量法舒地尔组在 ISO 注射前分别用 3mg/kg/天和 10mg/kg/天治疗 4 周。在 ISO 注射后第 4 周测量心功能，称体重和全心重。通过 HE 染色分析梗死面积和厚度。此外，通过检测血清 CK 和 LDH，以及实时聚合酶链反应（PCR）和 Western blot 检测取出的心脏组织，来测量心肌损伤程度。
在 MI 组，心功能明显下降：左心室短轴缩短率（FS）和左心室射血分数（EF）明显降低，左心室容积明显增加，心肌损伤标志物 CK 和 LDH 明显增加。此外，法舒地尔治疗以剂量依赖性方式显著缓解 MI 后的心脏功能，减轻心肌细胞氧化损伤，抑制细胞凋亡。
法舒地尔可通过抑制 Rho/ROCK 信号通路减少 ISO 诱导的 MI，减少心肌细胞氧化损伤，抑制细胞凋亡。
