双靶点注射6-OHDA建立帕金森病大鼠模型并提高成功率  

The PD rat model were established by the injection 6-OHDA into SNC and VTA with stereotactic technique

作　　者：牛朝诗[1] 杨艳艳[1,2] 

机构地区：[1]安徽医科大学附属省立医院神经外科,合肥230001 [2]中国人民解放军105医院神经外科

出　　处：《立体定向和功能性神经外科杂志》2008年第5期257-262,共6页Chinese Journal of Stereotactic and Functional Neurosurgery

基　　金：安徽省科技攻关项目(编号:01013030);安徽省优秀青年科技基金项目(编号:04043072);安徽省人才开发基金项目(编号:2006Z037)

摘　　要：目的建立大鼠帕金森病模型,观测其行为学、中脑黑质多巴胺能神经元及超微结构的变化。方法利用立体定向技术,注射6-OHDA至大鼠中脑黑质SNc和中脑腹侧被盖区VTA,于注射后2、4、6、8周观测阿朴吗啡诱导的大鼠旋转行为学变化;采用免疫组化染色检测TH的表达,了解中脑黑质多巴胺能阳性神经元变化;利用透射电镜了解黑质区超微结构的变化。结果所有大鼠进行阿朴吗啡诱导旋转行为测试,旋转圈数>7r/min,并且>210r/30min,为合格的PD大鼠模型。大鼠模型于第4、6和8周时,大鼠行为学变化较为恒定。第8周时,50只大鼠中出现32只大鼠大鼠旋转次数平均为11.5±1.2/分,造模成功率为64%。PD模型大鼠超微结构观察,黑质神经元数目明显减少,线粒体肿胀,粗面内质网囊性扩张、脱颗粒,髓鞘扩张。免疫组化检测,成功模型光镜下分别计数双侧黑质TH阳性神经元,损毁侧黑质TH阳性神经元占正常侧的3.0%,即毁损侧TH阳性神经元减少97.0%。结论利用立体定向技术,选择黑质和中脑腹侧被盖区等双靶点,可建立6-OHDA大鼠PD模型,具有明确病理变化,提高模型成功率。Objective To establish Parkinson＇s disease rat model and observe the changes of behaviors, nigra dopaminergic neuron of PD rat model. Methods Build up Parkinson＇s disease model rat by direct injection 6-OHDA into substantia nigra pars compacta （SNc）and ventral tegmental area （VTA） with stereotactic technique. Apomorphine （0. 5mg/kg） injected celiac to evocate circle behavior. The changes of nigra dopaminergic neuron in the model were examined with immunohistochemistry. The uhrastructure＇s alteration were observed by transmission electron microscope. Results 6-OHDA was injected into the SNc and VTA in rat brain. A total 66, 7% of the rats rotated over 210 turns per 30 min after 8 week of 6--OHDA lesions. The immunohis- tochemical staining showed a significant reduction of TH--positive neurons in the 6--OHDA in- jection side compared with the opposite side. Pathological changes of the substantia nigra were found in the side, which included swelling and partial vacuoles of mitochondria, dilation of granular endoplamic reticulum and myelination. Conclusion PD model rats can be built up by direct two-sites injecting 6--OHDA with the stereotactic technique. It＇s efficiency are higher than one-site injecting. This model is similar to PD patient in physiological and biochemical feature.

关 键 词：立体定向技术 帕金森病 6-羟基多巴胺 大鼠 动物模型 超微结构 

分 类 号：R742.5[医药卫生—神经病学与精神病学] Q95[医药卫生—临床医学]