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脑缺血后溶酶体功能障碍致自噬流损伤机制的研究进展

王佳倩, 何红云, 邓仪昊^*

昆明理工大学基础医学院解剖学教研室，昆明 650500

摘要

缺血性脑卒中是由脑血管阻塞引发的急性脑血管病，是导致人类死亡和残疾的第三大原因。多项研究已证明缺血性脑卒中发生后自噬在神经元中起到积极的作用。自噬是细胞内介导各种底物转运至溶酶体降解和再循环的主要机制，其降解功能主要是通过溶酶体来实现的，故保持溶酶体功能正常对自噬十分重要。然而脑缺血会导致严重的溶酶体功能受损，进而引发自噬流障碍，加重神经元损伤。本文详细阐述缺血性脑卒中后由自噬体-溶酶体融合减少、溶酶体酸性环境发生改变以及溶酶体生物合成减少三个方面诱发的溶酶体功能障碍导致自噬流损伤的机制，以期通过增强溶酶体功能调节脑缺血后神经元自噬流，发挥神经保护作用，为治疗脑卒中提供新的思路。

关键词： 缺血性脑卒中; 神经元; 溶酶体功能障碍; 自噬流损伤

Research progress on the mechanism of autophagy flow injury caused by lysosomal dysfunction after cerebral ischemia

WANG Jia-Qian, HE Hong-Yun, DENG Yi-Hao^*

Department of Anatomy, Faculty of Medicine, Kunming University of Science and Technology, Kunming 650500, China

Abstract

Ischemic stroke is an acute cerebrovascular disease caused by cerebral vascular obstruction, which is the third leading cause of human death and disability. Multiple studies have demonstrated that autophagy plays a positive role in neurons after ischemic stroke. Autophagy is the main intracellular mechanism that mediates the degradation and recycling of various substrates in lysosomes, so it is very important to maintain normal function of lysosomes. However, cerebral ischemia can result in significant impairment of lysosomal function, subsequently leading to disruption in autophagy flow and exacerbation of neuronal injury. This review elucidates the mechanism of autophagic flux injury resulting from lysosomal dysfunction induced by impaired fusion between autophagosomes and lysosomes, alterations in the acidic environment within lysosomes, and diminished biosynthesis of lysosomes following ischemic stroke. The lysosome is regarded as the primary focal point for investigating the mechanism of autophagic flux injury, with the aim of modulating neuronal autophagic flux to improve cerebral ischemia-induced brain injury. This approach holds potential for exerting a neuroprotective effect and providing a novel avenue for stroke treatment.

Key words: ischemic stroke; neuron; lysosome dysfunction; autophagy flow injury

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通讯作者：邓仪昊　　E-mail:

引用本文：

王佳倩, 何红云, 邓仪昊. 脑缺血后溶酶体功能障碍致自噬流损伤机制的研究进展[J]. 生理学报 2024; 76 (5): 783-790.

WANG Jia-Qian, HE Hong-Yun, DENG Yi-Hao. Research progress on the mechanism of autophagy flow injury caused by lysosomal dysfunction after cerebral ischemia. Acta Physiol Sin 2024; 76 (5): 783-790 (in Chinese with English abstract).