实用医学杂志2025，Vol.41Issue(23)：3659-3665,7.DOI:10.3969/j.issn.1006-5725.2025.23.005
慢性间歇性低氧通过钙超载激活内质网应激诱导海马神经元凋亡
Chronic intermittent hypoxia induces hippocampal neuronal apoptosis by activating endoplasmic reticulum stress via calcium overload
摘要
Abstract
Objective To investigate the effects of chronic intermittent hypoxia(CIH)on hippocampal neuronal injury in rats,and to clarify the role of endoplasmic reticulum(ER)stress-related apoptotic pathways.Methods Male Sprague-Dawley rats were randomly assigned to a control group(n=8)or a CIH group(n=8).The CIH group was exposed to intermittent hypoxia for 8 h/day over 8 weeks.Hippocampal neuronal morphology was examined by hematoxylin-eosin staining and transmission electron microscopy.Neuronal apoptosis was assessed using the TUNEL assay.Intracellular Ca²⁺ levels were measured by flow cytometry.The mRNA and protein expression of ER stress-related factors(GRP78,CHOP)and the apoptotic effector Caspase-3 were quantified by qPCR and Western blot.Results Compared with controls,rats in the CIH group exhibited marked hippocampal neuronal damage,including disrupted cytoarchitecture,cytoplasmic dissolution,and swollen rough ER.Ultrastructural analysis revealed nuclear deformation and organelle disruption.TUNEL assay demonstrated a significant increase in apoptotic cells(P<0.05).Flow cytometry showed elevated intracellular Ca²⁺ levels(P<0.05).GRP78,CHOP,and Caspase-3 were significantly upregulated at both mRNA and protein levels in the CIH group(all P<0.05).Conclusion CIH induces pronounced hippocampal neuronal injury and apoptosis in rats,associated with Ca²⁺ dysregulation and activation of ER stress-mediated apoptotic pathways.These findings provide experimental evidence for elucidating the mechanisms of OSAHS-related neuronal injury and identifying potential therapeutic targets.关键词
慢性间歇性低氧/钙超载/内质网应激/细胞凋亡Key words
chronic intermittent hypoxia/calcium overload/endoplasmic reticulum stress/apoptosis分类
医药卫生引用本文复制引用
李瑜,陈玉岚,连思念,王红..慢性间歇性低氧通过钙超载激活内质网应激诱导海马神经元凋亡[J].实用医学杂志,2025,41(23):3659-3665,7.基金项目
国家健康卫生委高血压诊疗研究重点实验室开放课题(编号:NHC Key Laboratory of Hypertension Clinical Re-search 2024-05) （编号:NHC Key Laboratory of Hypertension Clinical Re-search 2024-05）
