Dexmedetomidine mediates NR4A3/Foxp3 signaling pathway to improve postoperative cognitive dysfunction in aged rats
Objective To investigate the improvement effect of dexmedetomidine on postoperative cognitive dysfunction in aged rats and its possible mechanism.Methods Twenty-four SD rats were randomly divided into sham operation group,postoperative cognitive dysfunction(POCD)model group and dexmedetomidine group,with 8 rats in each group.The animal model of POCD was established by sevoflurane anesthesia and laparotomy.The cognitive impairment of rats in each group was evaluated at 24 h after operation by Zea-Longa score;the learning and memory ability of rats was detected by water maze.The hippocampal injury of rats was detected by HE and TUNEL staining.The distribution of Tregs/Th17 was detected by flow cytometry.The levels of transforming growth factor-β(TGF-β),interleukin(IL)-17 A,IL-23 and IL-35 in hippocampus of rats were detected by ELISA.The mRNA expression of NR4A3 and Foxp3 was detected by real-time quantitative PCR(RT-qPCR).The protein expression of Foxp3 and NR4A3 in hippocampus of rats were detected by Western blot.Results Dexmedetomidine could improve postoperative cognitive dysfunction,reduce brain tissue injury and reduce the apoptosis rate of neurons.The proportion of CD4+IL-17A+Th17 in dexmedetomidine group was lower than that in model group,and the proportion of CD4+CD25+Foxp3+Treg was higher than that in model group.Dexmedetomidine significantly reversed the changes of IL-17A,IL-23,TGF-β and IL-35 in hippocampus of rats in model group,and enhanced the mRNA and protein expression of NR4A3 and Foxp3.Conclusion Dexmedetomidine improves postoperative cognitive dysfunction in aged rats by regulating the immune imbalance of Tregs/Th17 through NR4A3/Foxp3 pathway.
dexmedetomidineNR4A3/Foxp3 pathwayimmune imbalance of Tregs/Th17cognitive dysfunction
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