中国比较医学杂志2026，Vol.36Issue(14)：24-32,9.DOI:10.3969/j.issn.1671-7856.2026.14.003
循环压力降低miR-126-3p甲基化增加内皮细胞外泌体神经保护作用
Cyclic pressure enhances the neuroprotective effect of endothelial cells-derived exosomes by regulating miR-126-3p promoter methylation
摘要
Abstract
Objective Endothelial cells(ECs)can enhance neuronal tolerance to hypoxia and ischemia through secreted factors;mechanical forces can influence ECs gene expression.This study investigated the effect of cyclic pressure on miR-126-3p expression in human microvascular endothelial cells(HMEC-1)and elucidated the role of DNA methylation in regulating miR-126-3p.The protective effect of exosomes derived from cyclic pressure-treated HMEC-1 on neuronal cells under oxygen-glucose deprivation conditions was also investigated.Methods HMEC-1 cells were exposed to five cycles of cyclic pressure(100/0 mmHg).RT-qPCR and bisulfite-modified DNA sequencing(BMDS)were used to detect miR-126-3p expression and its promoter DNA methylation levels,respectively.DNA Methyltransferase(DNMT)activity and global methylation levels were measured in HMEC-1 cells.SH-SY5Y cells were incubated with exosomes derived from HMEC-1 culture medium and subjected to OGD/R.SH-SY5Y cell viability and apoptosis were assessed using MTS assay and flow cytometry,respectively.Cell damage was evaluated by detecting spectrin and caspase-3 levels using Western blot.Results Cyclic pressure reduced DNMT activity(P<0.05),decreased miR-126-3p promoter region DNA methylation,and increased expression of miR-126-3p in HMEC-1 cells(P<0.05).Cyclic pressure-treated HMEC-1-derived exosomes reduced OGD/R-induced damage in SH-SY5Y cells(P<0.05).Conclusions Cyclic pressure treatment induced the expression of the neuroprotective molecule miR-126-3p in ECs by reducing DNA methylation.The high level of miR-126-3p in ECs-derived exosomes might be a key factor in reducing in vitro ischemia and hypoxia-induced neuronal cell damage.关键词
远隔缺血预适应/神经保护/miR-126-3p/内皮细胞/高压力Key words
remote ischemic preconditioning/neuroprotection/miR-126-3p/endothelial cells/high pressure分类
医药卫生引用本文复制引用
谭莉明,李卫,张邵菡,邵国,王小洁,杨文典..循环压力降低miR-126-3p甲基化增加内皮细胞外泌体神经保护作用[J].中国比较医学杂志,2026,36(14):24-32,9.基金项目
国家自然科学基金(82060337) （82060337）
深圳市科技计划项目基础研究面上项目(JCYJ20220531092412028,JCYJ20230807121306012) （JCYJ20220531092412028,JCYJ20230807121306012）
深圳市龙岗区医疗卫生科技计划项目(LGKCYLWS2023025) （LGKCYLWS2023025）
深圳市南山区卫生健康局(NSZD2024052). （NSZD2024052）
