锂盐靶向β-catenin缓解实验性自身免疫性脑脊髓炎的机制研究  

Mechanism of lithium-targeted β-catenin in amelioration of experimental autoimmune encephalomyelitis

作　　者：吴帆[1] 倪琛[2,3] 张晶晶[4] 王辉[1] 秦志海[3] 

机构地区：[1]新乡医学院,河南新乡453003 [2]郑州大学第一附属医院,河南郑州450052 [3]中国科学院生物物理研究所,北京100101 [4]广东医学院附属医院,广东湛江524001

出　　处：《广东医学院学报》2015年第3期247-250,共4页Journal of Guangdong Medical College

基　　金：国家自然科学基金重大项目(No.91229203);国家自然科学基金项目(No.31370824)

摘　　要：目的研究锂盐抑制实验性自身免疫脑脊髓炎(的机制。方法 EAE)使用神经髓鞘蛋白源性多肽MOG35-55诱导IFNγR缺陷小鼠发生EAE,并喂食含锂饲料,观察小鼠神经症状,组织病理观察脑和脊髓中炎症细胞浸润。IFN-γ、锂盐和小豆蔻明处理小鼠脑内皮细胞系b END.3,Western blot检测β表达。结果 -catenin锂盐激活内皮细胞中β-catenin信号。IFNγR缺陷小鼠喂食含锂饲料降低了小鼠脑部炎症相关的非典型症状和脊髓炎症相关的典型症状。停止锂处理后,IFNγR缺陷小鼠EAE症状开始增加。锂治疗减少小鼠脑和脊髓中炎症细胞浸润。结论锂盐激活β-catenin缓解实验性自身免疫性脑脊髓炎并不一定依赖IFNγR信号,但在IFNγR信号缺失后锂盐治疗作用失去长效性。Objective To investigate the mechanism of lithium in the inhibition of experimental autoimmune encephalomyelitis（EAE）. EAE models were established by myelin protein-derived MOG in IFNMethods 35-55 γR deficient mice and then fed with lithium. The neurological symptoms were observed and inflammatory infiltration in the brain and spinal cord was examined by histopathology. β-catenin expression in mouse brain endothelial cells b END.3 was determined by Western blot after treated with IFN-γ, lithium and cardamomin. Results Lithium activated the β-catenin signaling in b END.3 cells. The lithium feed ameliorated the brain inflammation-associated atypical symptoms and spinal cord inflammation-associated classic symptoms in IFNγR deficient mice. The EAE symptoms began to increase after lithium termination. Histopathology showed that lithium treatment reduced the inflammatory infiltration in the brain and spinal cord. Conclusion Lithium-activated β-catenin could not necessarily depend on the IFNγR signaling in the mitigation of EAE. However, the long-term therapeutic effect of lithium on EAE is absent when IFNγR signaling is deficient.

关 键 词：实验性自身免疫性脑脊髓炎 IFNγR Β-CATENIN 锂 

分 类 号：R741[医药卫生—神经病学与精神病学]