Activation of autophagy inhibits the activation of NLRP3 inflammasome and alleviates sevoflurane-induced cognitive dysfunction in elderly rats

激活自噬抑制NLRP3炎症小体的激活减轻七氟醚引起的老年大鼠认知功能障碍

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作者:Junjie Zhou #, Chao Zhang #, Xu Fang, Naixin Zhang, Xiaoxi Zhang, Zhaoqiong Zhu

Conclusions

The activation of autophagy suppressed the formation of NLRP3 inflammasomes. It also alleviated cognitive impairment in aged rats.

Results

We found that sevoflurane exposure affected learning and working memory ability in aged rats. We also observed microglia activation in the prefrontal cortex. NLRP3 protein expression was significantly upregulated after sevoflurane inhalation. NLRP3 inflammasome activation induced increased expression and mRNA expression of cleaved Caspase-1 and inflammatory cytokines IL-1β and IL-18, and increased secretion of peripheral proinflammatory cytokines. The inhibitor MCC950 was used to improve cognitive ability and inflammation in rats and inhibit the secretion of cytokines. In addition, we demonstrated that significant inhibition of autophagy (decreased LC3-II/I and increased P62) was accompanied by increased activation of NLRP3 inflammasomes and more severe neural cell damage. However, autophagy inhibitor rapamycin administration to activate autophagy resulted in the inhibition of NLRP3 inflammasomes, ultimately attenuating neuronal injury. Conclusions: The activation of autophagy suppressed the formation of NLRP3 inflammasomes. It also alleviated cognitive impairment in aged rats.

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