中药单体及复方调控PINK1/Parkin介导线粒体自噬对心肌缺血再灌注损伤的研究进展

Research advances on the regulation of PINK1/Parkin-mediated mitophagy by Chinese herbal monomers and compounds in myocardial ischemia-reperfusion injury

关键词:  心肌缺血再灌注  线粒体自噬  PINK1/Parkin  中医药

Key words:  myocardial ischemia-reperfusion  mitophagy  PINK1/Parkin  traditional Chinese medicine

摘要:

心肌梗死是冠状动脉斑块破裂导致灌注的血流急剧减少从而发生缺血性坏死，造成心肌的不可逆损伤。对于心肌梗死挽救的方法是进行及时有效的再灌注治疗，主要包括药物溶栓或者经冠状动脉进行介入治疗（PCI），是挽救心肌梗死患者生命的主要手段，虽能显著提升患者存活率，但不可避免地会诱发心肌缺血再灌注损伤（MIRI）。在MIRI过程中，活性氧（ROS）大量产生，发生氧化应激，线粒体损伤加重，诱发细胞死亡，因此及时清除受损的线粒体，保持一定的线粒体自噬水平可以保护心肌细胞。PINK1/Parkin通路在调控线粒体自噬、维护心肌细胞稳态方面发挥关键作用。随着中医药对治疗MIRI作用机制的深入研究，逐渐证实中医药对线粒体结构调控能够有效地改善MIRI损伤。且中医药具有多组分、多靶点、疗效显著等特点。不同类型的中药单体如糖苷类、生物碱类、酚苷类、酚类等，以及中药复方中的通阳祛痰法、益气活血法、温阳利水法等，通过不同机制调控PINK1/Parkin通路，发挥中医药对心肌保护的功效。因此本文旨在从调控PINK1/Parkin线粒体自噬的角度总结中医药单体和复方心肌缺血再灌注损伤的研究进展，以期为MIRI的治疗提供新的中医药方法及思路。

Abstract:

Myocardial infarction（MI）occurs due to the rupture of coronary atherosclerotic plaques，leading to a sharp reduction in blood perfusion，resulting in ischemic necrosis and irreversible damage to the myocardium. The primary method to salvage MI is timely and effective reperfusion therapy，primarily including pharmacological thrombolysis or Percutaneous Coronary Intervention（PCI）. PCI is the main life-saving intervention for MI patients. Although it significantly improves patient survival rates，it inevitably induces Myocardial Ischemia-Reperfusion Injury（MIRI）. During MIRI，reactive oxygen species（ROS）are generated in large quantities，triggering oxidative stress. This exacerbates mitochondrial damage and induces cell death. Therefore，timely clearance of damaged mitochondria and maintaining an appropriate level of mitophagy are crucial for protecting cardiomyocytes. The PINK1/Parkin pathway plays a key role in regulating mitophagy and maintaining cardiomyocyte homeostasis. With deepening research into the mechanisms of Traditional Chinese Medicine（TCM）for treating MIRI，it has been gradually demonstrated that TCM can effectively ameliorate MIRI damage by regulating mitochondrial structure. TCM is characterized by its multi-component nature，multi-target actions，and significant therapeutic efficacy. Various types of Chinese herbal monomers（such as glycosides，alkaloids，phenolic glycosides，phenols）and TCM compound therapies categorized by their therapeutic principles（like Yang-unblocking phlegm-resolving therapy，qi-invigorating blood-activating therapy，yang-warming water-draining therapy）exert cardioprotective effects by regulating the PINK1 / Parkin pathway through different mechanisms. Therefore，this article aims to explore the regulation of PINK1 / Parkin-mediated mitophagy by Chinese herbal monomers and compounds，with the goal of providing new TCM-based methods and strategies for the treatment of MIRI.