脓毒症相关性脑病雄性小鼠学习记忆障碍与海马区α7nAChR表达及M1/M2型小胶质细胞比例有关

Cognitive impairments relate to the expression of α7 nicotinic acetylcholinergic receptor (α7nAChR) and the proportion of M1/M2 microglia in the hippocampus of male mice with sepsis-associated encephalopathy

目的 探索脓毒症相关性脑病(SAE)雌雄小鼠认知差异及其内在机制。方法 6~8周龄雌雄小鼠分别进行盲肠结扎穿刺术(CLP)诱导SAE模型,通过新物体识别和恐惧记忆实验检测小鼠学习记忆功能。采用免疫荧光组织化学染色法检测SAE雌雄小鼠海马区域α7烟碱型乙酰胆碱能受体(α7nAChR)表达和分布,M2型小胶质细胞比例,Western blot法检测α7nAChR蛋白水平。结果 SAE雄性小鼠学习记忆功能较SAE雌性小鼠明显降低,且SAE雄性小鼠海马区域α7nAChR蛋白表达水平较SAE雌性小鼠显著下降。同时海马区SAE雄性小鼠M2型小胶质细胞所占比例较雌性小鼠明显降低。结论 SAE雄性小鼠海马区域α7nAChR蛋白表达水平较SAE雌性小鼠显著下降,且M2型小胶质细胞比例相对降低,导致SAE雄性小鼠学习记忆功能障碍的发生。

Objective To investigate the cognitive differences between male and female mice with sepsis-associated encephalopathy(SAE) and its underlying mechanism. Methods The SAE model was induced by caecal ligation and puncture(CLP) in male and female mice aged from 6 to 8 weeks. The cognitive functions of the mice were evaluated by novel object recognition test and contextual fear conditioning test. The expression and distribution of α7 nicotinic acetylcholinergic receptor(α7nAChR) and the proportion of M2 microglia in hippocampus of SAE mice were detected by immunofluorescence staining, and the level of α7nAChR protein was detected by Western blot. Results The cognitive function of male SAE mice was significantly impaired, and the expression level of α7nAChR protein in hippocampus of male SAE mice decreased significantly compared with that of female SAE mice. At the same time, the proportion of M2 microglia in SAE male mice was significantly lower than that in female mice. Conclusion The expression level of α7nAChR protein in hippocampus of SAE male mice is significantly lower than that of SAE female mice, and the proportion of M2 microglia is relatively lower, which lead to the cognitive dysfunction of SAE male mice.