TEMPO improves cognitive dysfunction induced by sevoflurane in aged mice by regulating P2X4R/NLRP3 signaling pathway
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-1β and 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-1β and 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/NLRP3 pathway.
TEMPOsevofluranecognitive dysfunctionagedP2X4R/NLRP3 signal pathway
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