综述: 自噬参与心脏疾病调控的研究进展

细胞自噬(autophagy)是将细胞内受损、变性或衰老的蛋白质以及细胞器运输到溶酶体内进行消化降解的过程．细胞自噬既是一种广泛存在的正常生理过程，又是细胞对不良环境的一种防御机制，参与多种疾病的病理过程．正常水平的自噬可以保护细胞免受环境刺激的影响，但自噬过度和自噬不足却可能导致疾病的发生．在心脏中，心肌细胞自噬对维持心肌功能具有重要的作用，自噬的异常可能导致各种心肌疾病如溶酶体储积症(Danon disease)等．各种心血管刺激如心肌缺血(ischemia)、再灌注(reperfusion)损伤、慢性缺氧(chronic hypoxia)等均可诱导心肌细胞自噬增强．而这些情况下心肌细胞自噬的作用还不清楚：它是否是一种潜在的细胞存活机制还是导致细胞死亡或疾病发生的病理性机制，或者是同时具有两种作用，目前还没有定论．心脏疾病是心肌功能出现异常时产生的各种病理状态的总称．在多种心脏疾病中，均伴随有心肌细胞自噬的改变，且影响着疾病的发生发展．在心肌肥厚(hypertrophic cardiomyopathy)中，细胞自噬程度降低而加剧心肌肥厚；在心力衰竭(heart failure，HF)中，细胞自噬增强可导致心肌细胞自噬性死亡；而在心肌梗死(myocardial infarction，MI)中，细胞自噬增强可减小梗死面积．但是细胞自噬在心脏疾病中到底扮演着怎样的角色，取决于细胞自噬发生的水平及病理状态．目前越来越多的人开始关注药物与细胞自噬调节之间的联系，且主要集中于抗肿瘤药物及心血管调节药物的研究．另外，有报道维生素类以及雌激素受体拮抗剂他莫西芬对细胞自噬也具有调节作用．研究心肌细胞自噬与心脏疾病的关系，以及药物对细胞自噬的调节，将有利于从自噬的角度探讨心脏疾病的发生发展过程及机制，开发出治疗心脏疾病的药物．

Review: The Progress of Autophagy Involved in Heart Disease

Autophagy is a process in which damaged, modified or aging proteins and organelles are transported to the lysosome/vacuole for degradation. Autophagy is not only a widespread normal physiological process, but also a cell defense mechanism to adverse environment, involved in the pathological process of diseases. The normal level of autophagy can protect cells from environmental stimuli, however, continued excessive or insufficient autophagy could lead to disease. In the heart, myocardial autophagy plays a vital role to maintain myocardial function, but dysfunctional autophagy contributes to a diverse set of heart diseases, such as Danon disease. Multiple forms of cardiovascular stress can increase autophagic activity in cardiomyocytes, including chronic ischemia, reperfusion injury and Chronic hypoxia. The function of autophagy in these conditions is poorly understood: Does it serve a pro-survival function or contribute to disease pathogenesis, cell death, or both? Heart disease is the abnormal myocardia function when to produce a variety of pathological state. In the state of disease, cardiac autophagy degree will change, related to the occurrence and development of disease. As in Hypertrophic cardiomyopathy process, cell autophagy is reduced and aggravate myocardial hypertrophy. In heart failure process, autophagy increases can lead to cell death; And in myocardial infarction process, autophagy is enhanced and reduce the infarction area. But the real role of autophagy in the myocardium depending on the level of autophagic activation and the context in which it is induced. Currently, more and more people begin to pay close attention to the relationship between drugs and autophagy regulation, particularly on antitumor drugs and cardiovascular drugs. In addition, there are reports of estrogen receptor antagonists tamoxifen and vitamins also has a regulatory role for autophagy. To research of the relationship between autophagy and heart disease, and drugs on the regulation of autophagy will benefit for the occurrence and development of heart disease, and explore a new mechanism of drug treatment from the autophagy perspectives.