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缺血性脑卒中后神经元自噬流障碍的病理机制研究进展

刘继宇¹, 何红云^1,2, 邓仪昊^1,*

¹昆明理工大学基础医学院人体解剖学教研室，昆明 650500；²昆明理工大学附属安宁市第一人民医院，昆明 650399

摘要

自噬是一个将损伤细胞器、陈旧蛋白、多余胞质组分甚至病原体等通过自噬体呈递给溶酶体进行降解的细胞内代谢过程。它包括自噬启动、自噬体形成、自噬体-溶酶体融合和自噬底物在自噬溶酶体内降解和清除4个步骤。当这些过程呈连续通畅状态则可称为自噬流，自噬/溶酶体信号通路中某一或某些步骤发生阻滞均可导致自噬流障碍。众多研究表明，脑卒中后自噬流障碍是导致脑卒中后缺血半影区神经元损伤的重要原因。本文总结了缺血性脑卒中后神经元自噬流障碍的病理机制研究进展，并介绍了目前改善神经元自噬流障碍方法的研究进展，为深入探究脑卒中病理损伤机制提供参考。

关键词： 自噬; 缺血性脑卒中; 自噬溶酶体; 自噬流障碍; 病理机制

Pathogenic mechanisms of impaired neuronal autophagy flux after ischemic stroke

LIU Ji-Yu¹, HE Hong-Yun^1,2, DENG Yi-Hao^1,*

¹Department of Human Anatomy, Faculty of Medicine, Kunming University of Science and Technology, Kunming 650500, China；²Anning First People’s Hospital Affiliated to Kunming University of Science and Technology, Kunming 650399, China

Abstract

Autophagy is a metabolic process in which damaged organelles, obsolete proteins, excess cytoplasmic components, and even pathogens are presented to lysosomes for degradation via autophagosomes. It includes 4 processes: the initiation of autophagy, the formation of autophagosomes, the fusion of autophagosomes with lysosomes, and the degradation and removal of autophagic substrates within autophagic lysosomes. When these processes are continuous, it is called autophagy flux. Blockage of one or certain steps in the autophagy/lysosome signaling pathway can lead to impaired autophagy flux. Numerous studies have shown that impaired autophagy flux is an important cause of neuronal damage in the ischemic penumbra after stroke. This paper summarized research progress in the pathological mechanisms that cause impaired neuronal autophagy flux after ischemic stroke and discusses methods to improve neuronal autophagy flux, in order to provide a reference for an in-depth investigation of the pathological injury mechanisms after stroke.

Key words: autophagy; ischemic stroke; autophagic lysosomes; autophagic flow disorders; pathological mechanisms

收稿日期：　　录用日期：

通讯作者：邓仪昊　　E-mail: 20130117@kust.edu.cn

DOI: 10.13294/j.aps.2024.0004

引用本文：

刘继宇, 何红云, 邓仪昊. 缺血性脑卒中后神经元自噬流障碍的病理机制研究进展[J]. 生理学报 2024; 76 (1): 97-104.

LIU Ji-Yu, HE Hong-Yun, DENG Yi-Hao. Pathogenic mechanisms of impaired neuronal autophagy flux after ischemic stroke. Acta Physiol Sin 2024; 76 (1): 97-104 (in Chinese with English abstract).