BCL2家族蛋白在中药干预心肌缺血/再灌注损伤的作用研究进展

The role of BCL2 family proteins in traditional Chinese medicine intervention for myocardial ischemia/reperfusion injury

关键词:  BCL2家族蛋白  中药  心肌缺血再灌注损伤

Key words:  BCL2 family proteins  traditional Chinese medicine  ischemia-reperfusion injury

摘要:

心肌梗死（MI）及缺血再灌注损伤是导致冠心病患者死亡的重要因素。临床上常采用溶栓等多种方法治疗心肌梗死，但在缺血过程和血流恢复后，会导致心肌缺血/再灌注损伤（I/R）。中药具有多靶点协同、安全性良好等优势而被广泛用于I/R心肌保护，但其具体机制尚未十分清晰，限制了中药实现I/R心肌保护的进一步探索。靶向多途径信号抑制B淋巴细胞瘤-2（BCL2）家族蛋白调控的线粒体外膜通透性改变（MOMP）驱动型细胞凋亡（apoptosis）和线粒体通透性转换孔（MPTP）驱动型坏死性凋亡（necroptosis）是降低MI或I/R患者病死率的关键策略之一。目前尚无化学药或中药明确直接靶向BAK/BAX用于治疗I/R，而探索以BAK/BAX为靶标的中药，并发挥中药多靶点协同特性，可能是进一步发挥中药治疗I/R的有效方法。因此，针对I/R关键靶标BAK/BAX抑制剂缺乏、I/R治疗疗效局限的问题，文章综述了BCL2家族蛋白在中药干预I/R保护中的作用，提出了挖掘直接靶点抑制BAK/BAX蛋白的中药并进一步发挥中药多靶点协同增效减毒特性，从而实现心肌细胞保护的新策略。

Abstract:

Myocardial infarction（MI） and ischemia-reperfusion injury are significant factors leading to the death of patients with coronary heart disease. Although clinical interventions such as thrombolysis are routinely employed to treat MI，myocardial ischemia/reperfusion injury often occurs during ischemic episodes and subsequent blood flow restoration. Traditional Chinese medicine（TCM） has gained widespread application in myocardial protection against I/R due to its multi-target synergistic effects and favorable safety profile. However，the precise mechanisms underlying its therapeutic efficacy remain incompletely elucidated，hindering further exploration of TCM-based strategies for I/R myocardial protection. A pivotal approach to reducing mortality in MI or I/R patients involves targeting multiple signaling pathways to suppress B-cell lymphoma-2（BCL2） family protein-regulated mitochondrial outer membrane permeabilization（MOMP）-driven apoptosis and mitochondrial permeability transition pore（MPTP）-mediated necroptosis. Currently，neither conventional chemical drugs nor TCM agents have been conclusively identified to directly target BAK/BAX for I/R treatment. Exploring TCM compounds targeting BAK/BAX while leveraging their inherent multi-target synergistic properties may represent an effective strategy to advance TCM-based interventions for I/R. Therefore，addressing the lack of inhibitors targeting the key I/R molecule BAK/BAX and the limited efficacy of I/R treatments，this review discusses the role of BCL2 family proteins in CHM-mediated I/R protection and proposes a new strategy to identify CHMs that directly inhibit BAK/BAX proteins and formulate them based on traditional Chinese medicine theory，further leveraging the multi-target synergistic，efficacy-enhancing，and toxicity-reducing effects of CHMs for myocardial cell protection.