Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China.
Tohoku J Exp Med. 2012 Jul;227(3):161-70. doi: 10.1620/tjem.227.161.
Myocardial infarction (MI) leads to progressive left ventricular (LV) dilatation and is associated with interstitial fibrosis in the non-infarcted myocardium. The NF-κB signaling pathway plays an important role in ventricular remodeling after MI. Recent studies have indicated that the anti-malarial agent artemisinin can inhibit NF-κB activation, which may attenuate post-infarct myocardial remodeling. In this study, we investigated the effect of artemisinin on post-infarct myocardial remodeling using a rat model of MI. Adult male Sprague Dawley rats were divided into a sham group (n = 10) and MI groups that were treated either with oral gavage of artemisinin (75 mg/kg/day, n = 20) or vehicle (0.5% carboxymethyl cellulose, n = 20) three times a day for 4 weeks. Each treatment was started at 24 hours after ligation of the left anterior descending coronary artery. Four weeks after MI, the artemisinin-treated group showed a significantly improved survival rate compared with that of the vehicle-treated group (65% vs. 40%, P < 0.05). Although infarct size was similar in both groups, echocardiography showed significant improvements in cardiac function and left ventricular dimensions in the artemisinin-treated group. Moreover, the degree of myocardial fibrosis and elevated levels of fibrosis-related factors [transforming growth factor-β1, collagen type I, matrix metalloproteinase (MMP)-2 and MMP-9] in the non-infarcted myocardium were remarkably ameliorated by artemisinin (all P < 0.05). Importantly, artemisinin inhibited the NF-κB pathway by blocking IKBα phosphorylation. In conclusion, artemisinin may attenuate post-infarct myocardial remodeling by down-regulating the NF-κB pathway.
心肌梗死（MI）导致左心室（LV）进行性扩张，并与非梗塞心肌中的间质纤维化有关。NF-κB 信号通路在 MI 后心室重构中起重要作用。最近的研究表明，抗疟药青蒿素可以抑制 NF-κB 的激活，从而可能减轻梗塞后心肌重构。在这项研究中，我们使用 MI 大鼠模型研究了青蒿素对梗塞后心肌重构的影响。成年雄性 Sprague Dawley 大鼠分为假手术组（n = 10）和 MI 组，MI 组每天经口灌胃青蒿素（75 mg/kg/天，n = 20）或载体（0.5%羧甲基纤维素，n = 20）3 次，共 4 周。每种治疗方法均在结扎左前降支冠状动脉后 24 小时开始。MI 后 4 周，青蒿素治疗组的存活率明显高于载体治疗组（65% vs. 40%，P < 0.05）。尽管两组的梗塞面积相似，但超声心动图显示青蒿素治疗组的心脏功能和左心室尺寸均有明显改善。此外，青蒿素显著改善了非梗塞心肌中的心肌纤维化程度和纤维化相关因子[转化生长因子-β1、胶原 I、基质金属蛋白酶（MMP）-2 和 MMP-9]的升高（均 P < 0.05）。重要的是，青蒿素通过阻断 IKBα 磷酸化抑制 NF-κB 通路。总之，青蒿素可能通过下调 NF-κB 通路来减轻梗塞后心肌重构。
