陕西医学杂志2026，Vol.55Issue(9)：1185-1189,5.DOI:10.3969/j.issn.1000-7377.2026.09.004
七氟烷通过信号转导和转录激活因子5A/髓系细胞触发受体1轴激活NOD样受体热蛋白结构域相关蛋白3炎症小体介导小胶质细胞焦亡在衰老小鼠术后认知功能障碍中的作用
Sevoflurane activates the NLRP3 inflammasome via the STAT5A/TREM1 axis to mediate microglial pyroptosis in postoperative cognitive dysfunction in aged mice
摘要
Abstract
Objective:To investigate the mechanism by which sevoflurane activates the NLRP3 inflammasome via the STAT5A/TREM1 axis to mediate hippocampal microglial pyroptosis,thereby contributing to postoperative cognitive dysfunction(POCD)in aged mice.Methods:Aged C57BL/6 mice(18～20 months old)were randomly divid-ed into five groups:sham operation group,sevoflurane group,sevoflurane+STAT 5A inhibitor group,sevoflurane+TREM1 inhibitor group,and sevoflurane+NLRP3 inhibitor group.After sevoflurane anesthesia,cognitive function was as-sessed using the Morris water maze and novel object recognition tests.Western blot and immunohistochemistry were employed to detect microglial activation marker(Iba1),pyroptosis-related proteins(GSDMD-N,Caspase-1,IL-1β,IL-18),and the expression levels of molecules in the STAT5A/TREM1/NLRP3 axis in the hippocampus.Results:Compared with the sham operation group,the sevoflurane group showed significantly prolonged escape latency,a re-duced number of platform crossings,as well as reduced time spent in the target quadrant and recognition index(all P＜0.05)The number of Iba1-positive cells in the hippocampus,the expression levels of pyroptosis-related proteins and the expression levels of STAT5 A,TREM1,and NLRP3 were significantly increased(all P＜0.05).Compared with the sevoflurane group,inhibition of STAT5A led to significant decreases in TREM1,NLRP3,and pyroptosis in-dicators,along with improved cognitive function(all P＜0.05).Inhibition of TREM1 resulted in decreased NLRP3 and pyroptosis indicators(P＜0.05),but STAT5A expression remained high(P＞0.05).Inhibition of NLRP3 amel-iorated pyroptosis and cognitive function(all P＜0.05),but had no significant effect on STAT5A or TREM1 expres-sion(P＞0.05).No significant differences in cognitive function,pyroptosis indicators,or NLRP3 expression were ob-served among the three inhibitor groups(all P＞0.05).Conclusion:Sevoflurane activates STAT5A to upregulate TREM1 expression,which in turn activates the NLRP3 inflammasome,thereby inducing hippocampal microglial py-roptosis and leading to postoperative cognitive dysfunction in aged mice.关键词
七氟烷/信号转导和转录激活因子5A/髓系细胞触发受体1/NOD样受体热蛋白结构域相关蛋白3炎症小体/小胶质细胞焦亡/术后认知功能障碍/衰老小鼠Key words
Sevoflurane/STAT5A/TREM1/NLRP3 inflammasome/Microglial pyroptosis/Postoperative cog-nitive dysfunction/Aged mice分类
医药卫生引用本文复制引用
樊晓龙,高勇,王力,韩旭,田全发,孙玉琴..七氟烷通过信号转导和转录激活因子5A/髓系细胞触发受体1轴激活NOD样受体热蛋白结构域相关蛋白3炎症小体介导小胶质细胞焦亡在衰老小鼠术后认知功能障碍中的作用[J].陕西医学杂志,2026,55(9):1185-1189,5.基金项目
国家卫生健康委"十五五"规划全国重点课题(WSJK241122) （WSJK241122）
