2-BFI、阿米洛利和咪唑克生对实验性自身免疫性脑脊髓炎小鼠行为学和病理学变化的药效作用比较  

Comparison of the Pharmacodynamic Effect of 2-BFI, Amiloride, Idazoxan on Behavior and Pathological Changes of Experimental Autoimmune Encephalomyelitis Mice

作　　者：梁珊珊[1] 郑荣远[1] 厉芳[1] 刘银凤[1] 殷为勇[1] 王新施[1] 杨慧民[1] 

机构地区：[1]温州医科大学附属第一医院神经内科,325000

出　　处：《中国临床神经科学》2014年第3期252-257,共6页Chinese Journal of Clinical Neurosciences

基　　金：国家自然科学基金资助项目(编号:81070960)

摘　　要：目的比较3种咪唑啉Ⅱ类受体(I2R)高选择性配体2-(2-苯并呋喃基)-2-咪唑啉(2-BFI)、阿米洛利和咪唑克生对实验性自身免疫性脑脊髓炎(EAE)模型小鼠行为学和病理学变化的干预效果。方法在相同实验条件下,髓鞘少突胶质细胞糖蛋白35-55多肽诱导EAE小鼠模型后,分为空白对照组、EAE-生理盐水组、EAE-2-BFI组(2-BFI干预)、EAE-阿米洛利组(阿米洛利干预)、EAE-咪唑克生组(咪唑克生干预),每组8只。均采用经实验证实的有效剂量,用动物神经功能评分评价各组间小鼠行为学表现。苏木精-伊红染色和LFB髓鞘染色,观察中枢组织炎性细胞浸润和髓鞘脱失程度。结果 3个不同配体干预组小鼠的神经行为学和炎症病理学改变与EAE-生理盐水组比较均明显减轻,差异有显著统计学意义(P<0.01);而3个不同干预组之间的行为学和病理学变化比较无显著差异,2-BFI保护作用具微弱优势。结论 2-BFI、阿米洛利和咪唑克生均能明显减缓小鼠EAE发生与发展,均具有较好抑制中枢炎症反应的药理作用,3者间的药效作用强度未见明显差异。Aim To compare the pharmacodynamic effect of three kinds ofimidazole Ⅱ class receptor （I2R） high selectivity ligands 2-BFI,amiloride,idazoxan respectively on experimental autoimmune encephalomyelitis （EAE） mice at the same time and the same environmental conditions.Methods After the induction of C57BL/ 6 mice to EAE models,each group were given to a single use of 2-BFI,amiloride,idazoxan intervention （using the effective dose confirmed in the previous experiments）,adopted animal neurological score in HE staining and LFB myelin staining,observation and evaluation of the behavior of mice in each group,the inflammatory cells infiltration of central nervous system,demyelination extent.Results Three different ligands intervention groups compared with EAE-NS control group were significantly reduced on neurobehavioral and inflammatory pathological changes with a statistically significant difference.While among the three different intervention groups compared with each other,there was no significant difference on neurobehavioral and pathological changes,only 2-BFI group displayed a slight advantage of a protective effect.Conclusion 2-BFI,idazoxan and amiloride can significantly slow down both the occurrence and development of EAE mice,suggesting that the three imidazoline compounds have the role of suppressing central inflammatory response,but there is no significant difference in potency in the efficacy among the three groups.

关 键 词：2-(2-苯并呋喃基)-2-咪唑啉 阿米洛利 咪唑克生 实验性自身免疫性脑脊髓炎 

分 类 号：R744.5[医药卫生—神经病学与精神病学]