浙江医学2025，Vol.47Issue(22)：2388-2393,后插1,7.DOI:10.12056/j.issn.1006-2785.2025.47.22.2025-99
缺氧诱导因子-1α调控p53在蛛网膜下腔出血后细胞凋亡和脑水肿中的作用
HIF-1α in regulating roles of p53 in apoptosis and brain edema after subarachnoid hemorrhage
摘要
Abstract
Objective To investigate the regulation of hypoxia-inducible factor-1α(HIF-1α)in the role of p53 in early apoptosis and brain edema after subarachnoid hemorrhage(SAH).Methods Seventy-two healthy adult male SD rats were randomly divided into sham operation group(sham group),SAH group,and 2-methoxyestradiol(2ME2)group using a random number table method,each with 24 rats.The latter two groups were subjected to an intracarotid puncture method to establish an SAH animal model.At 24 hours after modeling,neurological function and SAH scores were evaluated in each group.Brain water content,blood-brain barrier permeability,apoptosis rate of brain tissues,and protein expression levels of HIF-1α,phosphorylated-p53(p-p53),Cleaved caspase-3,and matrix metalloproteinase-9(MMP-9)were measured using the wet-dry weight method,Evans blue staining,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assay,and Western blot,respectively.Results Compared with the sham group,the SAH group showed significantly decreased neurological function scores and protein expression levels of occludin and ZO-1 in brain tissues(all P＜0.05),while SAH scores,brain water content,blood-brain barrier permeability,apoptosis rate,and protein expression levels of HIF-1α,p-p53,Cleaved caspase-3,and MMP-9 were significantly increased(all P＜0.05).Compared with the SAH group,the neurological function scores and the expression levels of occludin and ZO-1 proteins in brain tissue of rats in the 2ME2 group were significantly increased(all P＜0.05),while the water content of brain tissue,the permeability of the blood-brain barrier,the apoptosis rate,and the protein expression levels of HIF-1α,p-p53,Cleaved-caspase-3,and MMP-9 were all significantly decreased(all P＜0.05).Conclusion HIF-1α may mediate the expression of downstream proteins,including cleaved caspase-3,MMP-9,occludin,and ZO-1 via regulating p-p53,and play a critical role in apoptosis and brain edema after SAH.关键词
蛛网膜下腔出血/缺氧诱导因子-1α/p53/细胞凋亡/脑水肿Key words
Subarachnoid hemorrhage/Hypoxia-inducible factor-1α/p53/Apoptosis/Brain edema引用本文复制引用
张蓉,杜权,俞文华,董晓巧,胡强..缺氧诱导因子-1α调控p53在蛛网膜下腔出血后细胞凋亡和脑水肿中的作用[J].浙江医学,2025,47(22):2388-2393,后插1,7.基金项目
浙江省医药卫生科技项目(2022KY244、2021KY235) （2022KY244、2021KY235）
杭州市医药卫生科技项目(A20251694) （A20251694）
