【摘要】 目的　探讨提高 6 羟基多巴胺帕金森病大鼠模型成功率的方法 ,并从行为学、黑质多巴胺神经元形态学角度对模型进行评价。方法　取SD大鼠 90只 ,将 6 羟基多巴胺立体定向微量注射于左侧黑质区及黑质纹状体通路 ,观察大鼠的行为及黑质细胞形态学变化。结果　① 90只大鼠中经阿朴吗啡诱导后有 6 4只 (占 71.1% )恒定转向右侧且结果稳定 ,旋转圈数>2 10r/ 30min ,被认为是成功的帕金森病大鼠模型 ;②除旋转行为外 ,部分大鼠还出现震颤、活动迟缓、嗅探、觅食、竖尾等异常表现 ;③随机选取 10只不同时期的成功帕金森病大鼠模型 ,免疫组化下观察发现注射侧黑质区多巴胺能神经元较对侧明显减少 (P <0 .0 0 1) ,电镜观察发现大鼠中脑黑质神经细胞普遍存在变性坏死及不同阶段的凋亡样改变。结论　用 6 羟基多巴胺选择性损毁黑质多巴胺能神经元可较快建立稳定的成功率较高的类似于人类中晚期帕金森病行为和病理的大鼠模型 ,但在病程和行为学等方面同帕金森病人仍有许多差异更多还原

【Abstract】 Objective To study the methods of heightening success rate of 6-OHDA-lesioned rats model for parkinson’s disease(PD) and evaluate the model from behavioral and morphology of nigra dopaminergic neurons(NDN).Methods The changes of behavior and NDN morphology were observed after stereotaxic microinjection of 6-hydroxydopamine(6-OHDA) into the left SNC and VTA in 90 Sprague Dawley(SD)rats.Result ①64 of 90 rats showed steadily right apormorphine-induced rotation(71.1%),its rotation rate above 210r/30min,which were regarded as success PD rats.②part of rats displayed abnormal behaviors such as trembling,moving stiffly,sniffing,seeking for food,railerection,et al.③ 10 success PD rat models of different period after operation were randomly chose.The immunohistochemical staining showed significant loss of TH-positive neurons in the injection place compared with opposite side.Observation under electron-microscope found that degeneration,necrosis and apoptosis existed extensively in mid-brain nigra neurons.Conclusions We can soon establish steady PD rat model of high success rate similar to PD of middle or later period in behavior and pathology through 6-OHDA-lesioned NDN,but there was some difference in some aspects such as behavior and course between the PD rat model and PD patient.更多还原