Study on a novel Rho kinase inhibitor WAR5 for treating EAE
10.3969/j.issn.1000-4718.2014.09.012
- VernacularTitle:新型 Rho 激酶抑制剂 WAR5治疗 EAE 的初步研究
- Author:
Zhibin DING
;
Hui ZHANG
;
Xingwang YANG
;
Haifei ZHANG
;
Jiezhong YU
;
Yanhua LI
;
Chunyun LIU
;
Wanfang YANG
;
Junlian LI
;
Qianjin FENG
;
Yongfei ZHAO
;
Baoguo XIAO
;
Cungen MA
- Publication Type:Journal Article
- Keywords:
WAR5 compound;
Fasudil;
Autoimmune encephalomyelitis,experimental;
Macrophages;
Nitric oxide synthase
- From:
Chinese Journal of Pathophysiology
2014;(9):1610-1615
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To explore the therapeutic effect of a novel Rho kinase inhibitor WAR 5 on the experimental autoimmune encephalomyelitis (EAE) and its possible mechanism.METHODS: Female C57BL/6 mice were randomly divided into EAE group and WAR5 group.EAE model was induced by the application of MOG 35-55 peptide.WAR5 was in-jected intraperitoneally every other day from post-immunization (PI) day 3 to PI day 27.The clinical score and body weight were recorded every other day .On PI day 28, the animals were sacrificed and spinal cords were obtained for HE and mye-lin staining .The splenocytes were isolated and the expression of CD 16/32 and CD206 were analyzed by flow cytometry . The protein extracts from the brains and spinal cords were collected for the measurement of inducible nitric oxide synthase ( iNOS) by Western blotting .RESULTS:The administration of WAR 5 delayed the onset of EAE and attenuated the clini-cal symptoms .The results of the pathological examination revealed that WAR 5 inhibited the infiltration of inflammatory cells and improved myelination in spinal cords , accompanied with the poralization of M 1 macrophages to M2 phenotype in the spleen.WAR5 inhibited the expression of iNOS in the central nervous system , especially in the spinal cords .CON-CLUSION:The therapeutic effect of WAR5 on EAE may be related to the shift of M1 macrophages to M2 phenotype and inhibition of inflammation in the central nerve system .
