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

doi:10.3969/j.issn.1006-5725.2025.23.005

Abstract

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.

Key words: chronic intermittent hypoxia, calcium overload, endoplasmic reticulum stress, apoptosis

CLC Number:

R592

Yu LI,Yulan CHEN,Sinian LIAN,Hong. WANG. Chronic intermittent hypoxia induces hippocampal neuronal apoptosis by activating endoplasmic reticulum stress via calcium overload[J]. The Journal of Practical Medicine, 2025, 41(23): 3659-3665.

Figures/Tables 7

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References 25

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指标	对照组	CIH	t值	P值
GRP78	0.583 ± 0.035	0.725 ± 0.055	-4.341	0.005
CHOP	0.313 ± 0.031	0.469 ± 0.048	-5.489	0.002
caspase-3	0.315 ± 0.067	0.672 ± 0.096	-6.083	0.001

Chronic intermittent hypoxia induces hippocampal neuronal apoptosis by activating endoplasmic reticulum stress via calcium overload

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