基于PINK1/Parkin通路探讨线粒体自噬防治心力衰竭作用及中医药治疗进展

Role of Mitophagy in Prevention and Treatment of Heart Failure Based on PINK1/Parkin Pathway and Treatment with Traditional Chinese Medicine:A Review

心力衰竭是一组复杂的临床综合征,为心血管疾病发展的终末阶段,死亡率极高,但由于病理机制复杂,目前还未寻找到一种十分有效的治疗方法。线粒体是细胞最为关键的细胞器之一,不仅在细胞内起着能量供应的重要作用,还广泛参与细胞的各项生命活动,如氧化应激的调节、细胞凋亡的调控等,线粒体功能的正常与否对维持机体正常生命活动具有重要意义。近年来,研究发现,线粒体的异常功能与多种疾病的发生和发展相关,其中与心力衰竭发病之间关系密切,线粒体稳态失衡是心肌细胞死亡,心力衰竭发病的关键因素,而线粒体自噬作为一种调控机体线粒体稳态的方式对防治心力衰竭具有重要意义。中医药疗法是我国独有治疗方式,现已广泛应用于临床当中,而其在治疗心力衰竭中疗效显著,具有独特优势。目前现代药理学研究表明,中药单体及复方能靶向调节心肌细胞线粒体稳态,影响线粒体自噬,保护心肌细胞,然机制尚不清楚。因此,该文从PTEN诱导假定激酶1(PINK1)/E3泛素蛋白连接酶(Parkin)通路出发探讨PINK1/Parkin通路在线粒体自噬及心力衰竭中的作用机制,并对PINK1/Parkin通路介导的线粒体自噬对心力衰竭的影响进行综述,同时结合中医药探讨其对PINK1/Parkin介导线粒体自噬对心力衰竭的治疗作用,旨在从PINK1/Parkin调控线粒体自噬角度为中医药防治心力衰竭提供新的思路与方法。

Heart failure is a group of complex clinical syndromes that represent the final stage of cardiovascular disease development,characterized by an extremely high mortality rate.However,due to the complexity of the pathological mechanisms,an effective treatment method has not yet been found.Mitochondria are among the most critical organelles in cells,playing an essential role in energy supply and widely participating in various life activities,such as the regulation of oxidative stress and apoptosis.The normal functioning of mitochondria is crucial for maintaining the body's normal life activities.In recent years,studies have found that mitochondrial dysfunction is associated with the occurrence and progression of various diseases,particularly closely related to the onset of heart failure.An imbalance in mitochondrial homeostasis is a key factor in cardiomyocyte death and the onset of heart failure.Mitochondrial autophagy,as a means of regulating mitochondrial homeostasis,is significant for the prevention and treatment of heart failure.Traditional Chinese medicine(TCM)therapy is a unique treatment approach in China now widely applied in clinical practice,demonstrating significant efficacy in treating heart failure,with unique advantages.Modern pharmacological research indicates that Chinese medicine monomers and compounds can target and regulate mitochondrial homeostasis in cardiomyocytes,affect mitochondrial autophagy,and protect cardiomyocytes,though the specific mechanisms remain unclear.Therefore,this paper explored the mechanisms of the PTEN-induced putative kinase 1(PINK1)/Parkin pathway in mitochondrial autophagy and heart failure,reviewed the effects of PINK1/Parkin-mediated mitochondrial autophagy on heart failure,and discussed the therapeutic effects of PINK1/Parkin-mediated mitochondrial autophagy on heart failure in conjunction with TCM.This paper is expected to provide new ideas and methods for the prevention and treatment of heart failure from the perspective of PINK1/Parkin regulation of mitochondrial autophagy.