α-FMH抑制小胶质细胞的活化改善大鼠相关炎症与认知功能障碍  

α-FMH alleviates LPS-induced inflammation and cognitive impairment in rats by inhibiting the activation of microglia

作　　者：侍崇龙 董洪权[1] 金文杰[1] SHI Chonglong;DONG Hongquan;JIN Wenjie(Department of Anesthesiology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院麻醉科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2021年第4期516-521,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金青年项目(81701375);江苏省自然科学基金青年项目(BK20171088)。

摘　　要：目的:在体探究组氨酸脱羧酶抑制剂α-FMH对脂多糖(lipopolysaccharide,LPS)引起的大鼠相关炎症及认知功能障碍的影响。方法:48只SD雄性大鼠随机分为4组,每组12只,分别为Control组、α-FMH组、LPS组、α-FMH+LPS组。在立体定位仪下行大鼠右侧侧脑室置管,恢复1周后置于逃避恐惧实验仪器中学习。然后将α-FMH或等体积的生理盐水定向注入大鼠右侧侧脑室,给药后30 min行LPS(1 mg/kg)腹腔注射,1 d后行为学实验评估大鼠的逃避恐惧能力;免疫组化检测海马区小胶质细胞的活化情况;ELISA法检测白介素-6和肿瘤坏死因子-α的表达量。结果:大鼠腹腔注射LPS后6 h海马区组胺表达明显增多,24 h内皆高于基础水平。与Control组相比,LPS组大鼠海马区小胶质细胞活化及上述炎症因子的表达均增加(P<0.01),且LPS组大鼠的僵立时间明显降低(P<0.01)。与LPS组相比,α-FMH+LPS组大鼠海马区小胶质细胞活化及炎症因子的表达明显降低(P<0.01),且α-FMH+LPS组大鼠的僵立时间明显增加(P<0.01)。结论:组氨酸脱羧酶抑制剂α-FMH通过抑制小胶质细胞的活化改善LPS诱导的大鼠相关炎症与认知功能障碍。Objective:To explore the effects of histidine decarboxylase inhibitors on lipopolysaccharide(LPS)-induced inflammation and cognitive impairment in rats in vivo.Methods:Forty-eight SD male rats were randomly divided into 4 groups with 12 rats in each group:control group,α-FMH group,LPS group andα-FMH+LPS group.Catheters were placed in the right lateral ventricle of rats with a stereotactic instrument,and a week after recovery,they were placed in an escape fear experimental instrument to learn.Thenα-FMH and the same volume of normal saline were directionally injected into the lateral ventricle of rats.Half an hour after administration,LPS(1 mg/kg)was injected intraperitoneally.A day later,the ability of rats to escape fear was evaluated by behavioral experiments.The activation of microglia in the hippocampus was detected by immunohistochemistry.The expression of interleukin 6 and tumor necrosis factorαwas detected by ELISA method.Results:After intraperitoneal injection of LPS,the expression of histamine in hippocampus began to increase significantly at 6 h,and was higher than the basic level within 24 h.Compared with the control group,the activation of microglia and the expression of inflammatory factors mentioned above in the hippocampus of the LPS group were increased(P<0.01),and the freezing time of the LPS group was significantly decreased(P<0.01).Compared with LPS group,the activation of microglia and the expression of the inflammatory factors in the hippocampus ofα-FMH+LPS group were significantly decreased(P<0.01),and the freezing time ofα-FMH+LPS group was significantly increased(P<0.01).Conclusion:Histidine decarboxylase inhibitorα-FMH can alleviate LPS-induced inflammation and cognitive impairment in rats by inhibiting the activation of microglia.

关 键 词：α-FMH 小胶质细胞 白介素-6 肿瘤坏死因子-Α 组胺 脂多糖 

分 类 号：R742[医药卫生—神经病学与精神病学]