兰州大学学报（医学版）2026，Vol.52Issue(3)：16-23,8.DOI:10.13885/j.issn.2097-681X.T20260026
AMPK/mTOR信号通路介导的自噬在模拟高海拔视网膜病变中的作用
Role of AMPK/mTOR signaling-mediated autophagy in simulated high-altitude retinopathy
摘要
Abstract
Objective To investigate the function of autophagy regulated by the AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway in simulated high-altitude retinopathy(HAR)and to explore its potential mechanisms.Methods Male C57BL/6 mice aged 6～8 weeks were employed.Mice in the model group were exposed to a hypobaric hypoxia chamber for 24 hours to simulate an altitude of approximately 5 000 m,and those in the control group were maintained under normal conditions.Histopathological changes in retinal tissues were assessed using hematoxylin-eosin staining.Reactive oxygen species levels were detected by dihydroethidium fluorescence staining.The expression of 8-OHdG in retinal tissue was examined by immunofluorescence.Western blotting analysis was performed to evaluate apoptosis-related proteins,including Bcl-2,Bax,and cleaved caspase-3(C-caspase 3),as well as key components of the AMPK/mTOR signaling pathway,including AMPK,mTOR and their phosphorylated forms.In addition,the expression of autophagy-related proteins LC3B and P62 was assessed by Western blotting and further con-firmed by immunofluorescence.Results Compared with the control group,mice exposed to simulated high-altitude conditions exhibited marked pathological alterations in retinal tissues.Dihydroethidium fluorescence staining revealed a significant increase in reactive oxygen species levels in the model group.Immunofluores-cence analysis showed a marked elevation of 8-OHdG expression.Western blotting results demonstrated sig-nificantly increased expression of Bax and C-caspase 3,indicating enhanced apoptotic activity.Phosphoryla-tion of AMPK was reduced,whereas phosphorylation of mTOR was increased in the model group.Moreover,LC3B expression was decreased and P62 expression was accumulated,suggesting a disturbance of autophagic flux.Conclusion Dysregulation of AMPK/mTOR-mediated autophagy may represent an important molecular mechanism underlying HAR.关键词
高海拔视网膜病变/AMPK/mTOR信号通路/自噬/氧化应激/细胞凋亡Key words
high-altitude retinopathy/AMPK/mTOR signaling pathway/autophagy/oxidative stress/apoptosis分类
医药卫生引用本文复制引用
叶强,王浩,赵安生,卢佳佳,胡笳乐,张文芳..AMPK/mTOR信号通路介导的自噬在模拟高海拔视网膜病变中的作用[J].兰州大学学报（医学版）,2026,52(3):16-23,8.基金项目
朗视界·沐光明中青年眼科科研项目(BCF-KH-YK-20240906-03) （BCF-KH-YK-20240906-03）
兰州大学第二医院萃英学子科研培育计划资助项目(CYXZPT2025-04,CYXZ2023-09) （CYXZPT2025-04,CYXZ2023-09）
甘肃省科技计划资助项目(24JRRA1105) （24JRRA1105）
