基于铁死亡通路探讨谷胱甘肽对七氟醚暴露新生小鼠脑损伤相关指标的影响  

Effect of glutathione on brain injury related indexes of newborn mice exposed to sevoflurane based on iron death pathway

作　　者：刘红霞 苗振华 牛会杨 石海涛 LIU Hongxia;MIAO Zhenhua;NIU Huiyang;SHI Haitao(Department of Hand Anesthesia,Xingtai Municipal Central Hospital,Xingtai,Hebei 054000,China)

机构地区：[1]河北省邢台市中心医院手麻科,河北邢台054000

出　　处：《检验医学与临床》2024年第19期2892-2897,共6页Laboratory Medicine and Clinic

基　　金：河北省邢台市重点研发计划自筹项目(2022ZC193)。

摘　　要：目的基于铁死亡通路探讨谷胱甘肽(GSH)对七氟醚暴露新生小鼠脑损伤相关指标的影响。方法将80只出生6 d的SPF级健康雌性小鼠分为对照组、单纯七氟醚组、GSH干预组和丁硫氨酸亚砜胺(BSO)干预组,每组20只;单纯七氟醚组、GSH干预组和BSO干预组采用七氟醚干预,对照组不采用七氟醚干预,在采用七氟醚干预前GSH干预组注射GSH 400 mg/kg,BSO干预组注射BSO 600 mg/kg;观察各组小鼠行为学及神经功能缺损情况,检测海马组织中Tau蛋白5(Tau5)、载脂蛋白E(ApoE)、PHF1、AT8蛋白表达水平及脑组织中谷胱甘肽过氧化物酶4(GPX4)、胱氨酸/谷氨酸逆向转运蛋白(xCT)及核因子-红系2相关因子2(Nrf2)蛋白水平,采用比色法检测小鼠脑组织匀浆上清液中铁离子、MDA及GSH水平,利用Perls染色法检测小鼠脑组织中铁沉积情况,并进行HE染色分析小鼠脑部病理学改变情况。结果GSH干预组小鼠逃避潜伏期、神经功能缺损评分明显低于单纯七氟醚组,穿越平台次数明显高于单纯七氟醚组,差异均有统计学意义(P<0.05)。GSH干预组小鼠海马组织Tau5、ApoE、PHF1、AT8蛋白水平及脑组织铁离子、MDA水平均明显低于单纯七氟醚组(P<0.05);GSH干预组脑组织GSH水平及GPX4、xCT及Nrf2蛋白水平均明显高于单纯七氟醚组(P<0.05)。光学显微镜下显示,GSH干预组小鼠脑组织中铁沉积明显少于单纯七氟醚组。HE染色显示,与单纯七氟醚组和BSO干预组相比,GSH组脑组织炎症浸润、细胞坏死、细胞水肿等现象显著减弱,且细胞排列间隙出现明显改善。结论利用GSH干预可有效通过铁死亡通路促进七氟醚暴露新生小鼠脑损伤的修复,并改善铁代谢相关指标。Objective To investigate the effect of glutathione(GSH)on brain injury related indexes of newborn mice exposed to sevoflurane based on iron death pathway.Methods Eighty healthy female mice with SPF grade on 6 d of birth were selected and divided into the control group,simple sevoflurane group,GSH intervention group and sulfonamide sulfonamide(BSO)intervention group,20 mice in each group.The simple sevoflurane group,GSH intervention group and BSO intervention group adopted the sevoflurane intervention,the control group did not adopt the sevoflurane intervention.Before adopting sevoflurane intervention,the GSH group was injected by 400 mg/kg GSH and the BSO intervention group was injected by 600 mg/kg BSO.The behavioral and neurological deficits of mice in each group were observed.The expression levels of Tau protein 5(Tau5),apolipoprotein E(ApoE),PHF1,AT8 in hippocampal tissues,and glutathione peroxidase 4(GPX4),cystine/glutamate antiporter(xCT),and nuclear factor erythroid 2-related factor 2(Nrf2)proteins levels in brain tissue were detected.The iron ion,MDA and GSH levels in brain tissue homogenate supernatant were detected by colorimetric method,and the Perls staining was used to detect the iron deposition in mouse brain tissues.The HE staining was performed to analyze the brain pathological changes in mice.Results The evasion latency and neurological deficit scores in the GSH intervention group were significantly lower than those in the simple sevoflurane group,and the number of platform crossings was significantly higher than that in the simple sevoflurane group,and the differences were statistically significant(P<0.05).The protein levels of Tau5,ApoE,PHF1 and AT8 in the hippocampus of mice in the GSH intervention group,as well as the levels of iron ions and MDA in the brain tissue,were significantly lower than those in the simple sevoflurane group(P<0.05).The GSH level and GPX4,xCT,Nrf2 protein levels in the brain tissue of mice in the GSH intervention group were significantly higher than those in the simple

关 键 词：铁死亡通路 谷胱甘肽 七氟醚 新生小鼠 脑损伤 

分 类 号：R363.13[医药卫生—病理学] R446.8[医药卫生—基础医学]