摘要
目的探讨右美托咪定是否可调节NRF2/NLRP3信号通路来改善脑出血大鼠血脑屏障和脑水肿。方法将大鼠分为Sham组、Model组、右美托咪定低剂量组(YMTMD-L)、右美托咪定高剂量组(YMTMD-H)和YMTMD-H+HY-N2485(NLRP3激活剂)组。Zea-Longa评分法评估大鼠神经功能;伊文思蓝(EB)检测大鼠血脑屏障通透性;检测大鼠脑含水量;电镜观察大鼠血脑屏障超微结构;TUNEL染色法检测海马神经元凋亡率;ELISA法检测大鼠海马组织TNF-α、IL-10和IL-1β水平;Western Blot检测大鼠海马组织闭合蛋白(Occludin)、闭锁连接蛋白-1(ZO-1)、紧密连接蛋白-5(Claudin-5)、基质金属蛋白酶(MMP-2、MMP-9)、NRF2、NLRP3、cleaved caspase-3蛋白表达。结果与Sham组相比,Model组大鼠血管内皮结构被破坏,神经功能评分、EB渗出率、脑含水量、神经元凋亡率、海马组织TNF-α和IL-1β水平、MMP-2、MMP-9、NLRP3和cleaved caspase-3蛋白表达水平显著升高,海马组织中IL-10水平、Occludin、Claudin-5、ZO-1、NRF2蛋白表达水平显著降低(P<0.05);与Model组相比,YMTMD-L和YMTMD-H组大鼠血管内皮损伤明显减轻,神经功能评分、EB渗出率、脑含水量、神经元凋亡率、海马组织TNF-α和IL-1β水平、MMP-2、MMP-9、NLRP3和cleaved caspase-3蛋白表达水平显著降低,海马组织中IL-10水平、Occludin、Claudin-5、ZO-1、NRF2蛋白表达水平显著升高(P<0.05);HY-N2485可减弱YMTMD对ICH大鼠血脑屏障和脑水肿的改善作用。结论YMTMD通过调控NRF2/NLRP3信号通路可减轻ICH大鼠炎症反应、脑水肿、脑损伤,改善血脑屏障和神经功能。
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 apoptosis rate of hippocampal neurons.TNF-α,IL-10,and IL-1βin hippocampal tissue were detected by ELISA.The expression of occludin,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 function score,EB exudation rate,brain water content,neuronal apoptosis rate,hippocampal tissue TNF-αand 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 endothelial damage in rats,the neurological function score,EB exudation rate,brain water content,neuronal apoptosis rate,hippocampal tissue TNF-αand IL-1β,MMP-2,MMP-9,NLRP3,and cleaved caspase-3 protein were greatly reduced.IL-10,Occludin,Claudin-5,ZO-1,and NRF2 protein expression in hippocampal tissue were greatly increased(P<0.05).HY-N2485 was able to weaken the improvement effects of YMTMD on the blood-brain barrier and brain edema in ICH rats.Conclusion YMTMD could alleviate 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.
作者
赵燕
王强
王萃
张敏
王稳
Zhao Yan;Wang Qiang;Wang Cui(Department of Anesthesiology,Department of Neurosurgery,Department of Oncology,the Second People's Hospital of Hengshui,Hengshui,Hebei 053000,China)
出处
《四川医学》
2025年第6期635-640,共6页
Sichuan Medical Journal
基金
衡水市科技计划项目(编号:2020014067Z)。
