中国临床药理学与治疗学2018，Vol.23Issue(1)：1-7,7.DOI:10.12092/j.issn.1009-2501.2018.01.001
咪唑克生减缓大鼠实验性自身免疫性脑脊髓炎脑损伤的保护作用时间窗研究
Therapeutic time window of effectiveness for idazoxan ameliorating brain damage of rats with experimental autoimmune encephalomyelitis
摘要
Abstract
AIM:To investigate the effective therapeutic time window of idazoxan in rats with experimental autoimmune encephalomyelitis (EAE).METHODS:Fifty SD rats were randomly divided into four groups:(1) Control group (n =8),which was given no treatment,but raised in the same condition as the experimental groups.(2) EAE-NS group (n =14),which received saline rather than idazoxan;(3) EAE-idazoxan 1-7 d group (n =14),which idazoxan was given at 2 mg/kg through i.p.(b.i.d.) from the first day of immunization to the 7th day;(4) EAE-idazoxan 8-14 d group (n =14),which received 2 mg/kg idazoxan through i.p.(b.i.d.) from the 8th day of immunization to the 14th day.Rat's behavioral changes were measured twice daily after immunizations until they were killed at 15th day after immunization to collect the cerebrum and the lumbar spinal cord.HE staining and luxol fast blue (LFB) staining was performed on the tissue sections to show tissue damage,infiltration of inflammatory cells and demyelination.Immunohistochemistry was used to determine the expression of Ibal and GFAP in the spinal cord.RESULTS:Idazoxan improved neurological behaviours:EAE-idazoxan 8-14 d group significantly reduced the daily clinical scores and cumulative neurobehavioral scores compared with the EAE-NS group (P ＜0.05).Idazoxan reduced EAE histopathology:Inflammatory cell entry into the brain and spinal cord was significantly reduced in EAE-idazoxan 8-14 d group compared with the EAE-NS group (P ＜0.05).Demyelinationin the brain and spinal cord was also reduced in EAE-idazoxan 8-14 d group based on LFB staining when compared with EAE-NS group (P ＜ 0.05).Idazoxan reduced Iba1 expression:EAE induced significant increase in the number of Iba1 expressing cells in the brain and reduce astrocytic (GFAP) activation.Compared with the EAE-NS group,the number of Iba1 positive cells EAE-idazoxan 8-14 d Group was significantly reduced (P ＜0.01).ELISA analysis showed that the expressions of IL-17 (P ＜ 0.01) decreased and IL-10 increased significantly in the CNS in EAE-idazoxan 8-14 d group rats compared with EAE-NS group rats.CONCLUSION:The effective therapeutic time window for idazoxan is in the period of disease onset of EAE disease progression.The protective effect of idazoxan on EAE is associated with the attenuated microglial activation and shifting the balance of inflammatory cytokines.关键词
咪唑克生/实验性自身免疫性脑脊髓炎/小胶质细胞/炎性细胞因子Key words
idazoxan/experimental autoimmune encephalomyelitis/microglia/inflammatory cytokines分类
医药卫生引用本文复制引用
厉芳,郑浏璞,翁建龙,郭涛,宋兴伟,郑荣远..咪唑克生减缓大鼠实验性自身免疫性脑脊髓炎脑损伤的保护作用时间窗研究[J].中国临床药理学与治疗学,2018,23(1):1-7,7.基金项目
国家自然科学基金项目(81070960) （81070960）
浙江医学高等专科学校科研基金项目(2015XZBOT) （2015XZBOT）
