Hydrogen Sulfide Attenuates Myocardial Hypoxia-Reoxygenation Injury by Inhibiting Autophagy via mTOR Activation
Hydrogen Sulfide Attenuates Myocardial Hypoxia-Reoxygenation Injury by Inhibiting Autophagy via mTOR Activation
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DOI：
10.1159/000438597
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发表时间：
2015-12
影响因子：
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通讯作者：
Jian Xiao;Xiaoyan Zhu;B. Kang;Ji-bin Xu;Lihui Wu;Jiang Hong;Yufeng Zhang;X. Ni;Zhinong Wang
中科院分区：
文献类型：
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作者：
Jian Xiao;Xiaoyan Zhu;B. Kang;Ji-bin Xu;Lihui Wu;Jiang Hong;Yufeng Zhang;X. Ni;Zhinong Wang
背景：自噬在心肌缺血再灌注（IR）损伤中起重要作用。硫化氢（H2S）已被证明可保护心肌细胞免受IR损伤，但其是否具有抗自噬作用尚不清楚。本研究的目的是探讨H2S是否调节IR损伤中的自噬及其可能的机制。方法与结果：将新生大鼠心肌细胞随机分为Con、HR和H2S保护组。采用细胞活力（MTT）和乳酸脱氢酶（LDH）释放测定法评估细胞损伤程度，采用流式细胞术评估细胞自噬水平，检测自噬相关基因（Atg）表达，如Beclin1、LC3-II。在H2S的作用下，Beclin1和LC3-II蛋白下调，p-mTOR蛋白上调，细胞活力增加，LDH降低。此外，为了研究mTOR是否参与H2S的保护作用，我们将mTOR抑制剂雷帕霉素与NaHS和HR合用或不合用。发现雷帕霉素减弱H2S对心肌细胞的保护作用。为了证明自噬在HR损伤过程中的作用，我们用自噬抑制剂3-MA预处理心肌细胞，3-MA可以减轻细胞损伤。结论：H2S通过激活mTOR调控心肌自噬，对IR损伤具有心肌保护作用。
Background: Autophagy plays a significant role in myocardial ischemia reperfusion (IR) injury. Hydrogen sulfide (H2S) has been demonstrated to protect cardiomyocytes against IR injury, while whether it has anti-autophagy effect has not been known. The aim of this study was to investigate whether H2S regulates autophagy during IR injury and its possible mechanism. Methods and Results: The cardiomyocytes of neonatal rats were randomized into Con, hypoxia-reoxygenation (HR) and H2S protection groups. The severity of cell injury was evaluated by cell vitality (MTT) and lactate dehydrogenase (LDH) release assays, and autophagy level was evaluated by flow cytometry and the assessment of autophagy-related gene (Atg) expression, such as that of Beclin1 and LC3-II. In response to H2S, Beclin1 and LC3-II protein were found to be down-regulated and p-mTOR protein was found to be up-regulated, together with an increase in cell vitality and a decrease in LDH. Furthermore, to find out whether mTOR was involved in the protective effect of H2S, rapamycin, inhibiter of mTOR, was used with or without applying NaHS and HR. It was found that rapamycin attenuated the myocardiocyte protective effect of H2S. To demonstrate the effect of autophagy during HR injury, the cardiomyocytes were pre-treated with 3-MA, which is an autophagy inhibitor, cell injury was attenuated by 3-MA. Conclusions: H2S plays a myocardial protective role against IR injury by regulating autophagy via mTOR activation.