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Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction

机译:麝香酮对心肌梗塞小鼠模型心脏重构的有益作用

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摘要

Musk has been traditionally used in East Asia to alleviate the symptoms of angina pectoris. However, it remains unclear as to whether muscone, the main active ingredient of musk, has any beneficial effects on persistent myocardial ischemia in vivo. The aim of the present study was to investigate whether muscone can improve cardiac function and attenuate myocardial remodeling following myocardial infarction (MI) in mice. Mice were subjected to permanent ligation of the left anterior descending coronary artery to induce MI, and then randomly treated with muscone (2 mg/kg/day) or the vehicle (normal saline) for 3 weeks. Sham-operated mice were used as controls and were also administered the vehicle (normal saline). Treatment with muscone significantly improved cardiac function and exercise tolerance, as evidenced by the decrease in the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, as well as an increase in the left ventricular ejection fraction, left ventricular fractional shortening and time to exhaustion during swimming. Pathological and morphological assessments indicated that treatment with muscone alleviated myocardial fibrosis, collagen deposition and improved the heart weight/body weight ratio. Muscone inhibited the inflammatory response by reducing the expression of transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nuclear factor (NF)-κB. Treatment with muscone also reduced myocardial apoptosis by enhancing Bcl-2 and suppressing Bax expression. Muscone also induced the phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS). Our results demonstrate that muscone ameliorates cardiac remodeling and dysfunction induced by MI by exerting anti-fibrotic, anti-inflammatory and anti-apoptotic effects in the ischemic myocardium.
机译:传统上,东亚使用麝香来减轻心绞痛的症状。但是,尚不清楚麝香的主要活性成分麝香酮是否对体内持续的心肌缺血有任何有益作用。本研究的目的是研究muscone是否可以改善小鼠心肌梗死(MI)后的心脏功能并减轻其心肌重塑。对小鼠进行永久性结扎左冠状动脉前降支以诱导MI,然后将其随机给予muscone(2 mg / kg / day)或溶媒(生理盐水)3周。假手术小鼠被用作对照,并且还被给予了媒介物(生理盐水)。用muscone治疗可显着改善心脏功能和运动耐受性,左室收缩末期直径减小,左室舒张末期直径减小,左室射血分数增加,左室分数缩短和时间证明了这一点。游泳时筋疲力尽。病理和形态学评估表明,用麝香酮治疗可减轻心肌纤维化,胶原蛋白沉积并改善心脏重量/体重比。 Muscone通过降低转化生长因子(TGF)-β1,肿瘤坏死因子(TNF)-α,白介素(IL)-1β和核因子(NF)-κB的表达来抑制炎症反应。用麝香酮治疗还通过增强Bcl-2和抑制Bax表达来减少心肌细胞凋亡。 Muscone还诱导蛋白激酶B(Akt)和内皮一氧化氮合酶(eNOS)的磷酸化。我们的研究结果表明,麝香酮通过在缺血性心肌中发挥抗纤维化,抗炎和抗凋亡作用,改善了心肌梗死引起的心肌重塑和功能障碍。

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