四川医学2025，Vol.46Issue(6)：635-640,6.DOI:10.16252/j.cnki.issn1004-0501-2025.06.007
右美托咪定调节NRF2/NLRP3信号通路对脑出血大鼠血脑屏障和脑水肿的影响
Effects of Dexmedetomidine Regulating NRF2/NLRP3 Signaling Pathway on Blood-Brain Barrier and Cerebral Ede-ma in Rats with Cerebral Hemorrhage
摘要
Abstract
Objective To investigate whether dexmedetomidine regulate NRF2/NLRP3 signaling pathway to improve blood-brain barrier and cerebral edema in rats with cerebral hemorrhage(ICH).Methods Rats were separated into sham group,model group,dexmedetomidine low-dose group(YMTMD-L),dexmedetomidine high-dose group(YMTMD-H),and YMTMD-H+HY-N2485(NLRP3 activator)group.Zea-Longa scoring method was applied to evaluate the neural function of rats.Blood-brain barrier permeability was detected in rats by Evans blue(EB).The brain water content of rats was detected.Electron microscopy was applied to observe the ultrastructure of the blood-brain barrier in rats.TUNEL staining method was applied to detect the apop-tosis rate of hippocampal neurons.TNF-α,IL-10,and IL-1β in hippocampal tissue were detected by ELISA.The expression of oc-cludin,Claudin-5,ZO-1,MMP-2,MMP-9,NRF2,NLRP3,and cleaved caspase-3 proteins in hippocampal tissue were detected by Western Blot.Results Compared with sham group,vascular endothelial structure was destroyed in model group,neurological func-tion score,EB exudation rate,brain water content,neuronal apoptosis rate,hippocampal tissue TNF-α and IL-1β,MMP-2,MMP-9,NLRP3,and cleaved caspase-3 protein were greatly increased.IL-10,Occludin,Claudin-5,ZO-1,and NRF2 protein in hippocampal tissue were greatly reduced(P＜0.05).Compared with model group,YMTMD-L and YMTMD-H groups had greatly reduced endo-thelial damage in rats,the neurological function score,EB exudation rate,brain water content,neuronal apoptosis rate,hippocampal tissue TNF-α and IL-1β,MMP-2,MMP-9,NLRP3,and cleaved caspase-3 protein were greatly reduced.IL-10,Occludin,Clau-din-5,ZO-1,and NRF2 protein expression in hippocampal tissue were greatly increased(P＜0.05).HY-N2485 was able to weak-en the improvement effects of YMTMD on the blood-brain barrier and brain edema in ICH rats.Conclusion YMTMD could allevi-ate inflammation,brain edema,and brain injury in ICH rats by regulating the NRF2/NLRP3 signaling pathway,thereby improving the blood-brain barrier and neurological function.关键词
右美托咪定/NRF2/NLRP3信号通路/脑出血/血脑屏障/脑水肿/大鼠Key words
dexmedetomidine/NRF2/NLRP3 signaling pathway/cerebral hemorrhage/blood brain barrier/cerebral ede-ma/rat分类
医药卫生引用本文复制引用
赵燕,王强,王萃,张敏,王稳..右美托咪定调节NRF2/NLRP3信号通路对脑出血大鼠血脑屏障和脑水肿的影响[J].四川医学,2025,46(6):635-640,6.基金项目
衡水市科技计划项目(编号:2020014067Z) （编号:2020014067Z）
