Hydrogen Sulfide Promotes Cardiomyocyte Proliferation and Heart Regeneration via ROS Scavenging
Hydrogen Sulfide Promotes Cardiomyocyte Proliferation and Heart Regeneration via ROS Scavenging
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硫化氢通过清除 ROS 促进心肌细胞增殖和心脏再生
DOI：
10.1155/2020/1412696
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发表时间：
2020-05-22
影响因子：
--
通讯作者：
Chen, Xi
中科院分区：
文献类型：
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作者：
Pei, Jianqiu;Wang, Fang;Chen, Xi
新生小鼠心脏在损伤后21天内即可完全再生，为探索心脏再生治疗靶点提供了理想的模型。活性氧（Reactive Oxygen Species，ROS）引起的氧化损伤是心肌细胞（cardiomyocytes，CM）细胞周期阻滞的重要原因之一，导致小鼠心脏在出生后7天或更短时间内丧失再生能力。硫化氢（H2S）作为一种抗氧化剂，通过清除病理过程中产生的活性氧（ROS），在多种疾病中发挥保护作用。在这项研究中，我们发现，通过PAG（H2S合成酶抑制剂）阻断H2S的合成暂停心脏再生和CM增殖与ROS沉积增加后，心脏损伤（心肌梗死或心尖切除术）在2日龄小鼠。NaHS（H2S供体）给药改善了7日龄小鼠心肌梗死后CM增殖和ROS清除的心脏再生。NaHS通过清除SOD 2依赖的ROS保护H2O2诱导的原代新生小鼠CM凋亡并促进CM增殖。H_2S清除ROS后，CMs DNA氧化损伤程度减轻。我们的研究结果首次证明了H2S促进心脏再生，并将NaHS确定为心脏修复的有效调节剂。
Neonatal mouse hearts can regenerate completely in 21 days after cardiac injury, providing an ideal model to exploring heart regenerative therapeutic targets. The oxidative damage by Reactive Oxygen Species (ROS) is one of the critical reasons for the cell cycle arrest of cardiomyocytes (CMs), which cause mouse hearts losing the capacity to regenerate in 7 days or shorter after birth. As an antioxidant, hydrogen sulfide (H2S) plays a protective role in a variety of diseases by scavenging ROS produced during the pathological processes. In this study, we found that blocking H2S synthesis by PAG (H2S synthase inhibitor) suspended heart regeneration and CM proliferation with ROS deposition increase after cardiac injury (myocardial infarction or apex resection) in 2-day-old mice. NaHS (a H2S donor) administration improved heart regeneration with CM proliferation and ROS elimination after myocardial infarction in 7-day-old mice. NaHS protected primary neonatal mouse CMs from H2O2-induced apoptosis and promoted CM proliferation via SOD2-dependent ROS scavenging. The oxidative DNA damage in CMs was reduced with the elimination of ROS by H2S. Our results demonstrated for the first time that H2S promotes heart regeneration and identified NaHS as a potent modulator for cardiac repair.