TRIF在秋水仙素致小鼠纹状体-黑质轴突退变模型中的作用  

Effect of TRIF in the Mouse Models with Colchicine-induced Striatum-substantia Nigra Axonal Degeneration

作　　者：周红利[1] 林森[2] 李淑蓉[2] 孙静[2] 苏炳银[2] Zhou Hongli;Lin Sen;Li Shurong;Sun Jing;Su Bingyin(Chengdu Medical College, Chengdu 610500, China;Sichuan Province Key Laboratory of Development and Reproduction, Chengdu Medical College, Chengdu 610500, China)

机构地区：[1]成都医学院,成都610500 [2]成都医学院发育与再生四川省重点实验室,成都610500

出　　处：《成都医学院学报》2019年第5期557-561,共5页Journal of Chengdu Medical College

基　　金：国家自然科学基金项目(No:31540032);发育与再生四川省重点实验室研究基金项目(No:SYS15-006)

摘　　要：目的通过秋水仙素(colchicine,COL)构建小鼠纹状体-黑质轴突退变模型,探究TRIF对纹状体及中脑黑质炎症微环境的影响。方法选取TRIF基因敲除小鼠(TRIF小鼠)为实验组,具有相同遗传背景的C57BL/6小鼠(WT小鼠)为对照组,每组5只。用脑立体定位仪在纹状体部位注射秋水仙素,建立轴突退变模型。分别于建模成功后1、3、7、14d,比较两组动物的行为学改变;采用高效液相色谱(HPLC)检测该模型4个时间点纹状体中神经递质多巴胺(DA)及二羟苯乙酸(DOPAC)含量的变化。结果两组小鼠均出现震颤、肌肉僵直、转圈、运动迟缓等行为,成功构建小鼠纹状体-黑质轴突退变模型。实验组体重和游泳能力方面与对照组相比较,差异具有统计学意义(P<0.05)。实验组小鼠建模后的1、7d纹状体神经递质DA及DOPAC含量较对照组低(P<0.05)。结论TRIF小鼠比WT小鼠的纹状体-黑质神经元退变加重,提示TRIF可能具有神经保护作用。Objective To explore the effect of TRIF on the inflammatory microenvironment of striatum and midbrain substantia nigra by establishing the mouse models with colchicine-induced striatum-substantia nigra axonal degeneration. Methods The mice with the TRIF gene knocked out were selected into the experiment group and the C57BL/6 mice (WT mice) with the same genetic background were enrolled into the control group with 5 mice in each group. The mouse models with axonal degeneration were established by the colchicine injection at striatum with the stereotaxic apparatus. The behavioral changes of the mouse models in the two groups were observed and compared on the 1st, 3rd, 7th and 14th day after the successful establishment of the models with axonal degeneration. The contents of neurotransmitter dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in striatum were detected at the four designated time points by using high performance liquid chromatography (HPLC). Results The behaviors including tremor, muscle stiffness, circle rotation and slow movement occurred among the mice of the two groups, suggesting the successful establishment of the models with axonal degeneration. Weight and swimming ability in the experiment group were significantly different from those in the control group ( P< 0.05). The consents of DA and DOPAC in striatum on the 1st and 7th day after the successful establishment of the models with axonal degeneration were significantly less in the experiment group than in the control group ( P< 0.05). Conclusion The degeneration of striatum-substantia nigra neurons in the mice with the TRIF gene knocked out was more severe than that in the WT mice, which suggests that TRIF may have neuroprotective effect.

关 键 词：TRIF 秋水仙素 多巴胺能神经元 纹状体-黑质 轴突退变 

分 类 号：R364[医药卫生—病理学]