Antioxidant mechanism of Rutin on hypoxia-induced pulmonary arterial cell proliferation.
Antioxidant mechanism of Rutin on hypoxia-induced pulmonary arterial cell proliferation.
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DOI：
10.3390/molecules191119036
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发表时间：
2014-11-18
期刊：
影响因子：
--
通讯作者：
Zheng X
中科院分区：
文献类型：
--
作者：
Li Q;Qiu Y;Mao M;Lv J;Zhang L;Li S;Li X;Zheng X
活性氧（Reactive oxygen species，ROS）作为介导剂或诱导剂参与了肺动脉高压的病理过程。大黄素是一种黄酮类化合物，在体外和体内均表现出显著的清除氧自由基的特性。本研究认为芦丁通过清除活性氧抑制缺氧诱导的肺动脉平滑肌细胞增殖。免疫荧光结果显示，芦丁可抑制肺动脉内皮细胞（PAECs）内主要通过线粒体和NADPH氧化酶4（Nox 4）产生的ROS。Western blot结果进一步证实了芦丁可增加Nox 4和缺氧诱导因子-1 α（HIF-1α）的表达。流式细胞仪细胞周期分析表明，芦丁对缺氧诱导的PASMCs增殖也有抑制作用。然而，N-乙酰基-L-半胱氨酸（NAC），清除剂的ROS，取消或减少的能力，芦丁在抑制缺氧诱导的细胞增殖。这些数据表明，芦丁显示出对缺氧性肺动脉高压的发展，通过抑制ROS，随后防止缺氧诱导的PASMC增殖的潜在好处。
Reactive oxygen species (ROS) are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study, we proposed that rutin attenuated hypoxia-induced pulmonary artery smooth muscle cell (PASMC) proliferation by scavenging ROS. Immunofluorescence data showed that rutin decreased the production of ROS, which was mainly generated through mitochondria and NADPH oxidase 4 (Nox4) in pulmonary artery endothelial cells (PAECs). Western blot results provided further evidence on rutin increasing expression of Nox4 and hypoxia-inducible factor-1α (HIF-1α). Moreover, cell cycle analysis by flow cytometry indicated that proliferation of PASMCs triggered by hypoxia was also repressed by rutin. However, N-acetyl-L-cysteine (NAC), a scavenger of ROS, abolished or diminished the capability of rutin in repressing hypoxia-induced cell proliferation. These data suggest that rutin shows a potential benefit against the development of hypoxic pulmonary arterial hypertension by inhibiting ROS, subsequently preventing hypoxia-induced PASMC proliferation.
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