Abstract: Objective To investigate the role of mammalian target of rapamycin (mTOR) - autophagy pathway on microglia phenotype in hippocampus of septic mouse model. Methods Fifty-four male ICR mice were randomly allocated into three groups (n=18 for each group): Sham operation group (group Sham), cecal ligation and puncture group (group CLP)and CLP plus mTOR inhibitor rapamycin group (group CLP+Ra). Only laparotomy was performed in group Sham. Sepsis mouse model was performed by cecal ligation and puncture in group CLP. Rapamycin 1.5 mg / kg was injected intraperitoneally 6 hours before cecal ligation and puncture in group CLP+Ra. The enzyme-linked immunosorbent assay (ELISA) was conducted to assess the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-10 and transforming growth factor (TGF)-β in hippocampus. Immunofluorescence was used to calculate the number of ionized calcium binding adapter molecule (Iba) - 1 / CD86 and Iba-1 / CD206 positive microglia in hippocampal sections. The expression levels of phosphorylated mTOR (p-mTOR), microtubule associated protein 1 light chain 3Ⅱ (LC3Ⅱ) and Beclin-1 in hippocampus were detected by Western blot assay. Results Compared with group Sham, the levels of TNF-α, IL-1β, IL-10, TGF-β, the number of Iba-1 / CD86 and Iba-1 / CD206 positive microglia and the expression of p-mTOR were increased while the expression of LC3Ⅱ and Beclin-1 were decreased in group CLP (P＜0.05). Compared with group CLP, the levels of IL-10,TGF-β, the number of Iba-1/CD206 positive microglia and the expression of LC3Ⅱ and Beclin-1 were increased while the levels of TNF-α, IL-1β, the number of Iba-1/CD86 positive microglia and the expression of p-mTOR were decreased in group CLP+Ra (P＜0.05). Conclusion mTOR-autophagy pathway affects hippocampal inflammation in septic model mice by regulating microglial phenotype transformation.

Key words: sepsis, brain, hippocampus, microglia, autophagy, mTOR protein