Department of Ultrasonography Medicine, Suzhou Hospital of Traditional Chinese Medicine, 215009 Suzhou, China.
Suzhou Research Institute of Traditional Chinese Medicine, Suzhou Hospital of Traditional Chinese Medicine, 215009 Suzhou, China.
Oxid Med Cell Longev. 2021 Feb 1;2021:8865762. doi: 10.1155/2021/8865762. eCollection 2021.
Myocardial injury after cardiac arrest (CA) often results in severe myocardial dysfunction and death involving mitochondrial dysfunction. Here, we sought to investigate whether baicalin, a natural flavonoid compound, exerts cardioprotection against CA-induced injury via regulating mitochondrial dysfunction. We subjected the rats to asphyxia CA after a daily baicalin treatment for 4 weeks. After the return of spontaneous circulation, baicalin treatment significantly improved cardiac function performance, elevated survival rate from 35% to 75%, prevented necrosis and apoptosis in the myocardium, which was accompanied by reduced phosphorylation of Drp1 at serine 616, inhibited Drp1 translocation to the mitochondria and mitochondrial fission, and improved mitochondrial function. In H9c2 cells subjected to simulated ischemia/reperfusion, increased phosphorylation of Drp1 at serine 616 and subsequently enhanced mitochondrial Drp1 translocation as well as mitochondrial fission, augmented cardiomyocyte death, increased reactive oxygen species production, released cytochrome c from mitochondria and injured mitochondrial respiration were efficiently improved by baicalin and Drp1 specific inhibitor with Mdivi-1. Furthermore, overexpression of Drp1 augmented excessive mitochondrial fission and abolished baicalin-afforded cardioprotection, indicating that the protective impacts of baicalin are linked to the inhibition of Drp1. Altogether, our findings disclose for the first time that baicalin offers cardioprotection against ischemic myocardial injury after CA by inhibiting Drp1-mediated mitochondrial fission. Baicalin might be a prospective therapy for the treatment of post-CA myocardial injury.
心脏骤停（CA）后的心肌损伤常导致严重的心肌功能障碍和死亡，涉及线粒体功能障碍。在这里，我们试图研究黄芩素（一种天然黄酮类化合物）是否通过调节线粒体功能来发挥对 CA 诱导损伤的心脏保护作用。我们在每天给予黄芩素治疗 4 周后使大鼠发生窒息性 CA。自主循环恢复后，黄芩素治疗显著改善了心脏功能表现，将存活率从 35%提高到 75%，防止了心肌坏死和凋亡，同时减少了 Drp1 在丝氨酸 616 处的磷酸化，抑制了 Drp1 向线粒体的易位和线粒体分裂，并改善了线粒体功能。在模拟缺血/再灌注的 H9c2 细胞中，黄芩素和 Drp1 特异性抑制剂 Mdivi-1 可有效改善 Drp1 在丝氨酸 616 处的磷酸化增加以及随后增强的线粒体 Drp1 易位和线粒体分裂，增加心肌细胞死亡，增加活性氧物质的产生，从线粒体释放细胞色素 c 并损伤线粒体呼吸。此外，Drp1 的过表达增加了过多的线粒体分裂，并消除了黄芩素提供的心脏保护作用，表明黄芩素的保护作用与抑制 Drp1 有关。总之，我们的研究结果首次揭示，黄芩素通过抑制 Drp1 介导的线粒体分裂为 CA 后缺血性心肌损伤提供心脏保护。黄芩素可能是治疗 CA 后心肌损伤的一种有前途的治疗方法。
