四甲基哌啶氮氧自由基介导P2X4R/NLRP3信号通路改善七氟醚诱导老龄小鼠认知功能障碍  

TEMPO improves cognitive dysfunction induced by sevoflurane in aged mice by regulating P2X4R/NLRP3 signalingpathway

作　　者：杜薇 谢昕 李姣 张晓敏 黄泽清 DU Wei;XIE Xin;LI Jiao;ZHANG Xiao-min;HUANG Ze-qing(Department of Anesthesiology,Cancer Hospital of China Medical University,Liaoning Cancer Hospital&Insitute,Shenyang 110042,China)

机构地区：[1]中国医科大学肿瘤医院辽宁省肿瘤医院麻醉科,辽宁沈阳110042

出　　处：《解剖科学进展》2024年第1期86-89,共4页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(2023-BS-044)。

摘　　要：目的 探究四甲基哌啶氮氧自由基(TEMPO)对七氟醚诱导的老龄小鼠认知功能障碍的影响及机制。方法 将50只12月龄C57BL/6老年小鼠随机分为对照组、七氟醚组、TEMPO低、中和高剂量组,每组10只。Morris水迷宫实验检测小鼠学习和记忆能力;HE染色观察小鼠海马组织病理改变;TUNEL实验检测小鼠海马组织细胞凋亡;免疫荧光检测小鼠海马组织小胶质细胞标志物Iba-1;ELISA实验检测小鼠海马组织炎症因子TNF-α、IL-1β和IL-6表达;Western blot检测小鼠海马组织P2X4R和NLRP3蛋白表达水平。结果 给予TEMPO降低七氟醚诱麻醉的老龄小鼠逃避潜伏期,增加小鼠目标象限停留时间和穿越平台次数,改善小鼠海马组织病理损伤,降低小鼠海马组织细胞凋亡和小胶质细胞激活,下调小鼠海马组织TNF-α、IL-1β和IL-6水平及P2X4R和NLRP3蛋白表达水平。结论 TEMPO通过抑制P2X4R/NLRP3通路改善七氟醚麻醉诱导的老年小鼠海马组织病理损伤、神经细胞凋亡和神经炎症,改善小鼠认知功能障碍。Objective To investigate the effects of tetramethylpyridine nitrogen-oxide free radical(TEMPO)on sevoflurane-induced cognitive dysfunction in aged mice and the underlying mechanisms.Methods Fifty 12-month-old C57BL/6 aged mice were randomly divided into control group,sevoflurane group,and TEMPO low-dose,medium-dose and high-dose groups,with 10 mice in each group.The learning and memory ability of mice was detected by Morris water maze test;the pathological changes of hippocampal tissues were observed by HE staining;TUNEL test was used to detect the apoptosis of hippocampal tissues;Iba-1 was detected by immunofluorescence;TNF-α,IL-1βand IL-6 expressions in hippocampal tissues were detected by ELISA;and the protein expressions of P2X4R and NLRP3 in hippocampal tissues were detected by Western blot.Results TEMPO could reduce the escape latency of sevoflurane-induced anesthesia in aged mice,increase the time of staying in the target quadrant and the number of crossing the platform,improve the pathological damage of hippocampal tissues,reduce the apoptosis and microglial activation in hippocampal tissues,and down-regulate the levels of TNF-α,IL-1βand IL-6 and the protein expressions of P2X4R and NLRP3 in hippocampal tissues.Conclusion TEMPO can improve the pathological damage,apoptosis and neuroinflammation of hippocampal tissues in aged mice induced by sevoflurane anesthesia,and improve the cognitive dysfunction of mice by inhibiting the P2X4R/NLRP3pathway.

关 键 词：四甲基哌啶氮氧自由基 七氟醚 认知功能障碍 老龄 P2X4R/NLRP3信号通路 

分 类 号：R749.6[医药卫生—神经病学与精神病学]