2-(2-苯并呋喃基)-2-咪唑啉对实验性自身免疫性脑脊髓炎小鼠小胶质细胞活化及氧化应激的影响  

Effect of 2-( 2-benzo fu-ranyl)-2-imidazoline on microglial activation and oxidative stress in experimental autoimmune encephalomyelitis mice

作　　者：林福虹[1] 李炳尧 赵伟丽[1] 王洪权[1] 郑浏璞[3] 王沛[3] 郑荣远[3] LIN Fu-hong LI Bing-yao ZHAO Wei-li et al(Department of Neurology, Affiliated Hospital of Chifeng University, Chifeng 024005, Chin)

机构地区：[1]内蒙古自治区赤峰学院附属医院神经内科,024005 [2]赤峰市肿瘤医院 [3]温州医科大学附属第一医院神经内科

出　　处：《临床神经病学杂志》2016年第6期438-442,共5页Journal of Clinical Neurology

基　　金：国家自然科学基金(81070960)

摘　　要：目的：观察2-（2-苯并呋喃基）-2-咪唑啉（2-BFI ）对实验性自身免疫性脑脊髓炎（ EAE ）小鼠CNS小胶质细胞活化及氧化应激的影响。方法将27只C57BL／6小鼠随机分为正常对照组、EAE组和2-BFI干预组，每组9只。采用MOG35-55免疫法制作经典EAE模型。2-BFI干预组小鼠于EAE造模后当日起腹腔注射2-BFI 20 mg／kg，2次／d，连续14 d。正常对照组和EAE组以等量生理盐水代替。每日观察并记录动物行为学变化、进行神经功能缺损评分。免疫后第20 d处死各组小鼠，采用HE染色和LFB染色观察组织学变化；免疫组化法测定诱导型小鼠CNS中一氧化氮合成酶（iNOS）蛋白和离子钙接头分子（Iba-1）的表达，比色法检测丙二醛（ MDA）的含量；并对活化的小胶质细胞数量和iNOS蛋白表达水平进行线性相关分析。结果正常对照组小鼠未见神经系统受损的表现。与EAE组相比，2-BFI干预组日均神经功能缺损评分明显降低，CNS脊髓炎性细胞浸润明显减少，髓鞘脱失严重程度明显减轻，活化的小胶质细胞数量减少，iNOS蛋白表达明显减少，MDA含量降低（P＜0.05～0．01）。相关分析结果显示，iNOS表达水平与活化的小胶质细胞数量呈正相关（r＝0．596， P＜0.01）。结论2-BFI能减轻EAE小鼠临床症状和组织学改变，2-BFI对EAE小鼠的神经保护作用于小胶质细胞激活和减轻氧化应激相关。Objective To observe the effect of 2-（ 2-benzo fu-ranyl ）-2-imidazoline （ 2-BFI ） on microglial activation and oxidative stress in the CNS of experimental autoimmune encephalomyelitis （ EAE） mice.Methods Twenty-seven C57BL/6 mice were randomly divided into normal control group , EAE group and 2-BFI treatment group, with 9 mice in each group.EAE mice models were established by myelin oligodendrocyte glycoprotein （MOG35-55）.After immunization, 2-BFI treatment group were treated with an intraperitoneal injection of 2-BFI with 20 mg/kg, twice a day and for 14 d.While the mice in EAE group and normal control group were treated with an intraperitoneal injection of same amount of sodium chloride .The behavioural changes and the neural function defect scale of mice were daily examined .All the mice were killed at 20 d after immunization .Histological changes were detected by HE and LFB stain in the CNS tissue of mice .The immunohistochemical staining was used to measure the expression of induced nitric oxide synthase （iNOS）and calcium ion sub molecular （Iba-1） in the CNS of mice.The malonaldehyde （ MDA） level was measured by spectrophotometry .Results Normal control group showed no clinical signs.Compared with EAE group , max clinical score of 2-BFI treatment group was significantly decreased;2-BFI treatment group showed less inflammation infiltration in CNS; and the number of activated microglia cells , the expression of iNOS and the level of MDA were significantly decreased in 2-BFI treatment group （P〈0.05-0.01）. Relative analysis demonstrated that the expression of iNOS positively associated with microglial activation （r=0.596, P〈0.01） .Conclusions The treatment of 2-BFI could ameliorates clinical signs and histology change of EAE mice . The neuroprotection of 2-BFI on EAE mice associated with down-regulation microglial activation and alleviation oxidative stress.

关 键 词：实验性自身免疫性脑脊髓炎 2-(2-苯并呋喃基)-2-咪唑啉 小胶质细胞 诱导型一氧化氮合成酶 氧化应激 

分 类 号：R744.5[医药卫生—神经病学与精神病学]