雷沙吉兰对帕金森病小鼠模型炎症反应的影响  

EFFECT OF RASAGILINE ON INFLAMMATORY RESPONSE IN A MOUSE MODEL OF PARKINSON'S DISEASE

作　　者：王利平 张峥[1] 侯琳[1] 左金辉 李馨[2] WANG Li- ping, ZHANG Zheng , HOU Lin, ZUO Jinhui, LI Xin(Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao 266021, Chin)

机构地区：[1]青岛大学基础医学院生物化学与分子生物学实验室,山东青岛266021 [2]青岛大学细胞与分子生物学实验中心,山东青岛266021

出　　处：《青岛大学医学院学报》2017年第6期687-689,693,共4页Acta Academiae Medicinae Qingdao Universitatis

摘　　要：目的探讨雷沙吉兰对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病小鼠模型炎症反应的影响及其机制。方法将C57BL/6小鼠随机分为对照组、MPTP组、雷沙吉兰低剂量组和高剂量组。采用旋转法检测各组小鼠行为学的改变,采用免疫组织化学法检测多巴胺能神经元的损伤情况及小胶质细胞激活标志物iba1的表达,采用实时荧光定量PCR法检测一氧化氮合酶(iNOS)的表达。结果与对照组相比,MPTP组小鼠运动缓慢,黑质区有大量的多巴胺能神经元损伤,并伴有小胶质细胞的激活及iNOS的活性增加。与MPTP组相比,雷沙吉兰低剂量组和高剂量组小鼠运动障碍明显改善,黑质区多巴胺能神经元数量增加,活化的小胶质细胞减少,iNOS的表达降低。结论雷沙吉兰能抑制帕金森病模型小鼠黑质区小胶质细胞激活,降低iNOS的表达,从而抑制炎症反应。Objective To investigate the effect of rasagiline on inflammatory response induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）in a mouse model of Parkinson＇s disease and related mechanism. Methods C57 BL/6 mice were randomly divided into control group,MPTP group,and low-and high-dose rasagiline groups.The rotarod test was used to evaluate behavioral changes;immunohistochemistry was used to measure dopaminergic neuron injury and the expression of iba1,a marker for microglial activation;quantitative real-time PCR was used to measure the expression of inducible nitric oxide synthase（iNOS）. Results Compared with the control group,the MPTP group had slower movements and a higher degree of dopaminergic neuron injury in the substantia nigra with microglial activation and increased activity of iNOS.Compared with the MPTP group,the low-and high-dose rasagiline groups had a significant improvement in dyskinesia,an increase in the number of dopaminergic neurons in the substantia nigra,and reductions in the number of activated microglial cells and the expression of iNOS. Conclusion In a mouse model of Parkinson＇s disease,rasagiline can inhibit the activation of microglial cells in the substantia nigra,reduce the expression of iNOS,and thus inhibit inflammatory response.

关 键 词：雷沙吉兰 帕金森病 炎症 一氧化氮合酶 小鼠 

分 类 号：R-332[医药卫生] R742.5