雷帕霉素对小鼠实验性变态反应性脑脊髓炎大脑小胶质细胞活化的影响  

The Effect of Rapamycin on Activation of Cerebral Microglia in Experimental Autoimmune Encephalomyelitis Mice

作　　者：王莉 郑浏璞[1] 叶朦倩 郑荣远[1] 侯圣陶[1] WANG Li;ZHENG Liu-pu;YE Meng-qian;ZHENG Yong-yuan;HOU Shengtao(The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China)

机构地区：[1]温州医科大学附属第一医院,温州325000

出　　处：《中国临床神经科学》2019年第2期138-143,共6页Chinese Journal of Clinical Neurosciences

基　　金：温州市科技局项目(编号:Y20180740;国家自然科学基金项目(编号:81371321)

摘　　要：目的探讨雷帕霉素对小鼠实验性变态反应性脑脊髓炎(EAE)模型大脑小胶质细胞形态及功能的调节作用。方法小鼠进行EAE造模后分为两组:①生理盐水组(潜伏期腹腔注射生理盐水);②雷帕霉素组(潜伏期腹腔注射雷帕霉素1次/日)。于发病高峰期时处死小鼠取大脑,采用Iba1免疫荧光染色分析大脑皮质小胶质细胞数量及形态;real-time PCR法检测各组小鼠大脑皮质的肿瘤坏死因子α表达量。结果雷帕霉素治疗组与生理盐水组比较,小胶质细胞数明显下降(P <0. 01),形态向M2表型转换。雷帕霉素治疗组与生理盐水组比较,M1表型标记物诱导型一氧化氮合酶及分泌的肿瘤坏死因子α表达量显著下降(P <0. 01)。结论雷帕霉素能抑制小鼠EAE模型大脑小胶质细胞活化,且抑制M1表型小胶质细胞的促炎功能。Aim To investigate the regulation of rapamycin on the morphology and function of cerebral microglia in experimental autoimmune encephalomyelitis( EAE) mice. Methods The mice were divided into two groups after EAE modeling,a natural saline group with intra-abdominal injection of normal saline during the incubation,a rapamycin group with rapamycin injected once a day during the incubation. At the peak of the onset,the mouse brain was taken. The number and morphology of the cerebral cortex of the microglia were analyzed by Iba1 immunofluorescence staining. The expression of tumor necrosis factor-α( TNF-α) in the cerebral cortex of each group was detected by real-time PCR. Results After the rapamycin treatment,the number of microglia decreased significantly( P < 0. 01) compared with the natural saline group and the morphology changed to the M2 phenotype. The real-time PCR results showed that the rapamycin treatment group showed a significant decrease in the expression of the M1 phenotype marker inducible nitric oxide synthase( iNOS)( P < 0. 01) and the secreted proinflammatory factor TNF-α( P < 0. 01). Conclusion Rapamycin inhibits the activation of cerebral microglia in EAE mice and inhibits the proinflammatory function of M1 microglia.

关 键 词：实验性变态反应性脑脊髓炎 雷帕霉素 小胶质细胞 肿瘤坏死因子Α 诱导型一氧化氮合酶 

分 类 号：R744.51[医药卫生—神经病学与精神病学]