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Objectives: Neuro-inflammation induced by microglia is crucial in the pathogenesis of sepsis-associated encephalopathy (SAE). The endogenous lipid mediator, Resolvin D1 (RvD1), which is synthesized from docosahexaenoic acid, has been extensively reported to attenuate inflammation in various diseases by its anti-inflammation and pro-resolving functions. However, the effect of RvD1 on SAE remains unclear. In this study, we aimed to ex the function and mechanism of RvD1 on SAE mice. Methods: In our study, the SAE mice model was established by the method of cecal ligation and perforation (CLP). C57BL/6J mice were randomly divided into three groups: the Sham group, the CLP group and the CLP+RvD1 group. Cognitive impairment of the mice was assessed by Morris water maze. Iba1 immunohistochemistry was conducted to observe the activation of microglia in hippocampus of the mice from different groups. The production of cytokines, including TNF-α, IL-6 and IL-1β, and their mRNA levels were evaluated by ELISA and Q-PCR. The expression of the molecules from inflammatory signaling pathways was assessed by Western blot. Results: xaRvD1 treatment significantly improved the learning and cognitive ability of SAE mice. The activation of microglia and the production of inflammatory cytokines in hippocampal tissues were inhibited in CLP+RvD1 group. We also found that the inflammation of microglia was attenuated by RvD1 treatment both in vivo and in vitro. Moreover, the activation of NF-κB, MAPK and STAT signaling pathways were inhibited by RvD1 treatment, which partly explained the anti-inflammation function of RvD1 on SAE mice. Conclusions: RvD1 could improve the learning and cognitive ability of SAE mice by inhibiting the systemic and local inflammation. It could attenuate the inflammation in microglia by inhibiting the activation of inflammatory signaling pathways and then decreasing the production of cytokines. These findings are helpful to better understand the pathophysiology of SAE, which also provide a novel therapeutic method in clinic. |
