Department of Cardiology Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences, Beijing 100730, China.
Graduate School of Peking Union Medical College, Beijing, China.
Anal Cell Pathol (Amst). 2024 Aug 14;2024:8753898. doi: 10.1155/2024/8753898. eCollection 2024.
Shock wave therapy (SWT) is a new alternative therapy for patients with severe coronary artery disease that improves myocardial ischemic symptoms by delivering low-energy shock wave stimulation to ischaemic myocardium with low-energy pulsed waves. However, the specific mechanism of its protective effect is not fully understood, especially for the protective mechanism in cardiomyocytes after hypoxia/reoxygenation (H/R). We selected a rat H9c2 cardiomyocyte cell line to establish a stable H/R cardiomyocyte injury model by hypoxia/reoxygenation, and then used SWT for therapeutic intervention to explore its cardiomyocyte protective mechanisms. The results showed that SWT significantly increased cell viability and GSH levels while decreasing LDH levels, ROS levels, and MDA levels. SWT also improved mitochondrial morphology and function of cells after H/R. Meanwhile, we found that SWT could increase the expression of GPX4, xCT, and Bcl-2, while decreasing the expression of Bax and cleaved caspase-3, and inhibiting cardiomyocyte apoptosis and ferroptosis. Moreover, this protective effect of SWT on cardiomyocytes could be significantly reversed by knockdown of xCT, a key regulator protein of ferroptosis. In conclusion, our study shows that SWT can attenuate hypoxia-reoxygenation-induced myocardial injury and protect cardiomyocyte function by inhibiting H/R-induced apoptosis and ferroptosis, and this therapy may have important applications in the treatment of clinical myocardial ischemic diseases.
冲击波治疗（SWT）是一种治疗严重冠心病的新的替代疗法，通过向缺血心肌传递低能量脉冲波来改善心肌缺血症状。然而，其保护作用的具体机制尚不完全清楚，特别是对于缺氧/复氧（H/R）后心肌细胞的保护机制。我们选择大鼠 H9c2 心肌细胞系，通过缺氧/复氧建立稳定的 H/R 心肌细胞损伤模型，然后用 SWT 进行治疗干预，以探讨其心肌细胞保护机制。结果表明，SWT 可显著提高细胞活力和 GSH 水平，降低 LDH、ROS 和 MDA 水平。SWT 还改善了 H/R 后细胞的线粒体形态和功能。同时，我们发现 SWT 可以增加 GPX4、xCT 和 Bcl-2 的表达，降低 Bax 和 cleaved caspase-3 的表达，抑制心肌细胞凋亡和铁死亡。此外，SWT 对心肌细胞的这种保护作用可以通过敲低铁死亡的关键调节蛋白 xCT 而显著逆转。总之，我们的研究表明，SWT 可以通过抑制 H/R 诱导的细胞凋亡和铁死亡来减轻缺氧/复氧引起的心肌损伤，保护心肌细胞功能，这种治疗方法可能在治疗临床心肌缺血性疾病方面具有重要应用价值。
