Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, PR China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, PR China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, PR China; Department of Anesthesiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001, PR China.
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, PR China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, PR China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, PR China.
Phytomedicine. 2024 Oct;133:155900. doi: 10.1016/j.phymed.2024.155900. Epub 2024 Aug 1.
Although blood flow is restored after treatment of myocardial infarction (MI), myocardial ischemia and reperfusion (I/R) can cause cardiac injury, which is a leading cause of heart failure. Gastrodin (GAS) exerts protective effects against brain, heart, and kidney I/R. However, its pharmacological mechanism in myocardial I/R injury (MIRI) remains unclear.
GAS regulates autophagy in various diseases, such as acute hepatitis, vascular dementia, and stroke. We hypothesized that GAS could repair mitochondrial damage and regulate autophagy to protect against MIRI.
Male C57BL/6 mice and H9C2 cells were subjected to I/R and hypoxia-reoxygenation (H/R) injury after GAS administration, respectively, to assess the impact of GAS on cardiomyocyte phenotypes, heart, and mitochondrial structure and function. The effect of GAS on cardiac function and mitochondrial structure in patients undergoing cardiac surgery has been observed in clinical practice.
The effects of GAS on cardiac structure and function, mitochondrial structure, and expression of related molecules in an animal model of MIRI were evaluated using immunohistochemical staining, enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy, western blotting, and gene sequencing. Its effects on the morphological, molecular, and functional phenotypes of cardiomyocytes undergoing H/R were observed using immunohistochemical staining, real-time quantitative PCR, and western blotting.
GAS significantly reduces myocardial infarct size and improves cardiac function in MIRI mice in animal models and increases cardiomyocyte viability and reduces cardiomyocyte damage in cellular models. In clinical practice, myocardial injury was alleviated with better cardiac function in patients undergoing cardiac surgery after the application of GAS; improvements in mitochondria and autophagy activation were also observed. GAS primarily exerts cardioprotective effects through activation of the PINK1/Parkin pathway, which promotes mitochondrial autophagy to clear damaged mitochondria.
GAS can promote mitophagy and preserve mitochondria through PINK1/Parkin, thus indicating its tremendous potential as an effective perioperative myocardial protective agent.
尽管心肌梗死（MI）治疗后血流得到恢复，但心肌缺血再灌注（I/R）可导致心脏损伤，这是心力衰竭的主要原因。天麻素（GAS）对脑、心和肾 I/R 具有保护作用。然而，其在心肌缺血再灌注损伤（MIRI）中的药理机制尚不清楚。
天麻素在急性肝炎、血管性痴呆和中风等多种疾病中调节自噬。我们假设 GAS 可以修复线粒体损伤并调节自噬，从而防止 MIRI。
分别给予雄性 C57BL/6 小鼠和 H9C2 细胞天麻素后，使其发生 I/R 和缺氧复氧（H/R）损伤，以评估 GAS 对心肌细胞表型、心脏和线粒体结构和功能的影响。在临床实践中观察了 GAS 对接受心脏手术的患者心脏功能和线粒体结构的影响。
采用免疫组织化学染色、酶联免疫吸附试验（ELISA）、透射电子显微镜、Western blot 和基因测序评估 GAS 对 MIRI 动物模型中心脏结构和功能、线粒体结构以及相关分子表达的影响。通过免疫组织化学染色、实时定量 PCR 和 Western blot 观察 GAS 对 H/R 诱导的心肌细胞形态、分子和功能表型的影响。
在动物模型中，GAS 显著减少 MIRI 小鼠的心肌梗死面积并改善心脏功能，并在细胞模型中增加心肌细胞活力并减少心肌细胞损伤。在临床实践中，心脏手术患者应用 GAS 后心肌损伤减轻，心脏功能改善；还观察到线粒体和自噬激活的改善。GAS 主要通过激活 PINK1/Parkin 通路发挥心脏保护作用，从而促进线粒体自噬清除受损线粒体。
天麻素通过 PINK1/Parkin 促进线粒体自噬，从而保护线粒体，这表明其作为一种有效的围手术期心肌保护剂具有巨大潜力。
