改良6-OHDA注射法建立早期帕金森病大鼠模型  

The Establishment of Rat Model of Early Stage Parkinson's Disease by Improved Method with 6-OHDA Injection

作　　者：韩飞[1,2] 李成朋 魏操 杨梅[1,2] 周波[3] 张春林[3] 焦玲[4] 官志忠[1,2,5] 禹文峰[1,2] HAN Fei LI Chengpeng WEI Cao Yang Mei ZHOU Bo ZHANG Chunlin JIAO Ling GUAN Zhizhong YU Wenfeng(The Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang 550004, Guizhou, China The Education Ministry Key Laboratory of Endemic Diseases and Diseases of Ethenic Minority, Guizhou Medical University, Guiyang 550004, Guizhou, China Department of Biology, Guizhou Medical University, Guiyang 550004, Guizhou, China Department of Neurology of Affiliated Hospital, Guizhou Medical University, Guiyang 550004, Guizhou, China Department of Pathology, Guizhou Medical University, Guiyang 550004, Guizhou, China)

机构地区：[1]贵州医科大学分子生物学重点实验室,贵州贵阳550004 [2]贵州医科大学地方病与少数民族性疾病教育部重点实验室,贵州贵阳550004 [3]贵州医科大学生物教研室,贵州贵阳550004 [4]贵州医科大学附院神经内科,贵州贵阳550004 [5]贵州医科大学病理学教研室,贵州贵阳550004

出　　处：《贵州医科大学学报》2017年第3期258-262,共5页Journal of Guizhou Medical University

基　　金：国家自然科学基金(81360199);教育部科学技术研究项目(213032A);贵州省国际科技合作计划项目[批准号:黔科合外G字(2013)7026号];贵州省创新计划项目[黔教合协同创新中心(2014)06];贵州省教育厅项目(2015年贵州省普通高等学校地方病和少数民族疾病防控创新团队);贵州省科技计划课题任务书[黔科合重大专项字(2014)6008]

摘　　要：目的:改良6-羟基多巴胺(6-OHDA)立体定位注射法建立早期帕金森病(PD)大鼠模型。方法:40只雄性SD大鼠随机分为control组10只,model组30只;于手术前30 min,腹腔注射地昔帕明(25 mg/kg)及帕吉林(5 mg/kg),control组采用立体定位右侧纹状体注射生理盐水,model组注射6-OHDA;术后第3、4周采用圆筒测试及旋转测试测定大鼠的左前肢使用率和旋转速度,免疫组化方法检测黑质内酪氨酸羟化酶(TH)阳性神经元数量。结果:圆筒测试显示madel组大鼠左前肢使用率低于control组(P<0.01),旋转测试显示model组平均向左侧旋转速度(3.48圈/min),明显快于对照组(P<0.01),PD模型成功率为89.66%;免疫组化显示,model组右侧中脑黑质致密部(SNc)部位TH阳性神经元数目较control组右侧减少(44.81±2.89)%,差异有统计学意义(P<0.01),符合临床早期PD诊断标准。结论:改良的6-OHDA注射法建立早期PD大鼠模型简单易行,成功率高。Objective：To establish rat model of early stage of Parkinson＇s disease（ PD） with improved method of stereotactic injection of 6-OHDA. Methods：Forty male SD rats were randomly divided into control group（ group C,10 rats） and model group（ group PD,30 rats）. Desipramine（ 25mg/kg） and pargyline（ 5 mg/kg） were injected intraperitoneally 30 minutes before surgery,followed by stereotactic injection of saline（ control group） or 6-OHDA（ model group） in striatum. Cylinder test and rotation experiments were adopted to evaluate the behavior in 3 and 4 weeks after surgery. Immunohistochemical staining was adopted to analyze the positive cells of tyrosine hydroxylase（ TH） in substantia nigra compacta（ SNc）. Results：Cylinder test showed that the utilization rate of the left forelimb in group PD was lower than that in group C（ P〈0. 01）. Rotation experiments showed that the average number of turns in group PD was about 3. 48 turns/min while there was no rotation in group C（ P〈0. 01）. The success rate of PD model was 89. 66%. Immunohistochemistry showed TH positive neurons in right SNc of PD model decreased about 44. 81% compared with that of group C,which was in accordance with the criteria of early stage of PD. Conclusions：The improved method of 6-OHDA injection is a simple,feasible and highly successful approach to establish the model of early PD.

关 键 词：6-羟基多巴胺 帕金森病 大鼠 多巴胺神经元 酪氨酸羟化酶 

分 类 号：R741.02[医药卫生—神经病学与精神病学]