Allicin protects against cardiac hypertrophy and fibrosis via attenuating reactive oxygen species-dependent signaling pathways
Allicin protects against cardiac hypertrophy and fibrosis via attenuating reactive oxygen species-dependent signaling pathways
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大蒜素通过减弱活性氧依赖性信号通路来防止心脏肥大和纤维化
DOI：
10.1016/j.jnutbio.2009.11.001
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发表时间：
2010-12-01
影响因子：
5.6
通讯作者：
Li, Hongliang
中科院分区：
文献类型：
--
作者：
Liu, Chen;Cao, Feng;Li, Hongliang
氧化应激增加与慢性心肌肥厚和心力衰竭的发病机制有关。由于大蒜素在体外和体内都能抑制氧化应激，我们推测大蒜素可能通过阻断氧化应激依赖的信号传导来抑制心肌肥大。我们使用原代培养的心肌细胞和成纤维细胞以及一种成熟的心肌肥大动物模型来验证这一假设。结果表明，大蒜素能显著抑制血管紧张素Ⅱ或压力超负荷引起的肥大反应。大蒜素能显著抑制活性氧（ROS）的产生和NADPH氧化酶的活性。我们进一步的研究表明，这种抑制心肌肥厚的作用是通过阻断ROS依赖的ERK 1/2，JNK 1/2和AKT信号通路的激活介导的。另外的实验表明，大蒜素通过分别阻断核因子-κ B和Smad 2/3信号传导的激活来消除炎症和纤维化。这些效应的组合导致对心脏刺激的反应中保留的心脏功能。因此，这些研究结果表明，大蒜素保护心脏功能，并通过ROS依赖的机制，涉及多个细胞内信号，防止心肌肥厚的发展。(C)2010年爱思唯尔公司All rights reserved.
Increased oxidative stress has been associated with the pathogenesis of chronic cardiac hypertrophy and heart failure. Since allicin suppresses oxidative stress in vitro and in vivo, we hypothesized that allicin would inhibit cardiac hypertrophy through blocking oxidative stress-dependent signaling. We examined this hypothesis using primary cultured cardiac myocytes and fibroblasts and one well-established animal model of cardiac hypertrophy. Our results showed that allicin markedly inhibited hypertrophic responses induced by Ang II or pressure overload. The increased reactive oxygen species (ROS) generation and NADPH oxidase activity were significantly suppressed by allicin. Our further investigation revealed this inhibitory effect on cardiac hypertrophy was mediated by blocking the activation of ROS-dependent ERK1/2, JNK1/2 and AKT signaling pathways. Additional experiments demonstrated allicin abrogated inflammation and fibrosis by blocking the activation of nuclear factor-kappa B and Smad 2/3 signaling, respectively. The combination of these effects resulted in preserved cardiac function in response to cardiac stimuli. Consequently, these findings indicated that allicin protected cardiac function and prevented the development of cardiac hypertrophy through ROS-dependent mechanism involving multiple intracellular signaling. (C) 2010 Elsevier Inc. All rights reserved.