Irisin protects heart against-reperfusion injury through a SOD2-dependent mitochondria mechanism
Irisin protects heart against-reperfusion injury through a SOD2-dependent mitochondria mechanism
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鸢尾素通过 SOD2 依赖性线粒体机制保护心脏免受再灌注损伤
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发表时间：
2018
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通讯作者：
Chunyu Zeng
中科院分区：
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作者：
Zhen Wang;Ken Chen;Yu Han;Hua Zhu;Xinyu Zhou;Tao Tan;Jing Zeng;Jun Zhang;Yukai Liu;Yu Li;Yonggang Yao;Jianxun Yi;Duofen He;Jingsong Zhou;Jianjie Ma;Chunyu Zeng
鸢尾素是一种源自含纤维连接蛋白结构域5蛋白（FNDC5）的细胞外结构域的肌肉源蛋白，已被证明通过旁分泌作用调节线粒体福利。在这里，我们验证了鸢尾素通过保持心肌细胞线粒体功能有助于心肌梗死后心脏保护的假设。动物模型研究表明，静脉注射外源性鸢尾素对缺血/再灌注（I/R）引起的心脏损伤具有剂量依赖性的保护作用，表现为左心室射血分数的提高和血清cTnI水平的降低（n = 15, P < 0.05）。鸢尾素处理后I/ r诱导的心肌细胞凋亡减少。鸢尾素介导的保护作用至少在一定程度上对线粒体功能有影响，因为给药鸢尾素增加了梗死区线粒体中的鸢尾素染色。通过线粒体膜电位评价和超氧化物FLASH事件记录发现，鸢尾素还能降低I/ r诱导的氧化应激（n = 4, P < 0.05）。鸢尾素与超氧化物歧化酶e2 （SOD2）的相互作用在保护过程中起着关键作用，因为鸢尾素处理增加了SOD活性（n = 10, P < 0.05），恢复了心肌细胞中SOD2的线粒体定位（n = 5, P < 0.05）。这些结果表明鸢尾素对心脏I/R损伤具有保护作用。针对线粒体中鸢尾素的作用为心肌梗死提供了一种新的治疗干预手段。
Irisin, a muscle-origin protein derived from the extracellular domain of the fibronectin domain-containing 5 protein (FNDC5), has been shown to modulate mitochondria welfare through paracrine action. Here, we test the hypothesis that irisin contributes to cardioprotection after myocardial infarction by preserving mitochondrial function in cardiomyocytes. Animal model studies show that intravenous administration of exogenous irisin produces dose-dependent protection against ischemia/reperfusion (I/R)-induced injury to the heart as reflected by the improvement of left ventricular ejection fraction and the reduction in serum level of cTnI (n = 15, P < 0.05). I/R-induced apoptosis of cardiomyocytes is reduced after irisin treatment. The irisin-mediated protection has, at least in part, an effect on mitochondrial function because administration of irisin increases irisin staining in the mitochondria of the infarct area. Irisin also reduces I/R-induced oxidative stress as determined by mitochondrial membrane potential evaluation and superoxide FLASH event recording (n = 4, P < 0.05). The interaction between irisin and superoxide dismutase2 (SOD2) plays a key role in the protective process because irisin treatment increases SOD activity (n = 10, P < 0.05) and restores the mitochondria localization of SOD2 in cardiomyocytes (n = 5, P < 0.05). These results demonstrate that irisin plays a protective role against I/R injury to the heart. Targeting the action of irisin in mitochondria presents a novel therapeutic intervention for myocardial infarction.