帕金森病大鼠模型的行为学及神经元形态学评价

背景由于黑质致密部体积狭小,应用6-羟基多巴胺(6-Hydroxydopamine,6-OHDA)损毁黑质多巴胺神经元(Nigral dopaminergic neuron,NDN)制作帕金森病大鼠模型的成功率较低,一般仅为30%～40%左右.目的探讨帕金森病大鼠模型建立后的行为学及神经元形态学改变.设计完全随机的实验研究.地点和材料安徽省药物研究所,SD大鼠,6-OHDA,阿朴吗啡,兔抗TH血清,SR-6N大鼠脑立体定向仪等.干预将6-OHDA立体定向注射于90只SD大鼠的左侧黑质区及黑质纹状体通路,观察大鼠行为及多巴胺神经元形态学变化.主要观察指标旋转行为,震颤及其他异常行为,免疫组织化学观察,电镜观察.结果经阿朴吗啡诱导共筛选出64只成功大鼠模型(占71%);免疫组化观察发现注射侧黑质区NDN较对侧明显减少,电镜观察发现其普遍存在凋亡及坏死样改变.结论本方法是建立帕金森病大鼠模型的有效方法,在行为学和神经元形态学等方面同帕金森病人有许多相似之处.

Evaluation on behaviours and neuron morphology of Parkinson's disease rat model

BACKGROUND: The successful rate in the establishment of Parkinson' s disease(PD) model in rat is comparatively low through destroying Nigral dopaminergic neuron (NDN) by 6-hydroxydopamine (6-OJDA) because of the small volume of pars compacta of substantia nigra(SNC), which is only about 30% to 40%.OBJECTIVE: To discuss the changes on behaviour and neuron morphology after the establishment of PD rat model.DESIGN: A complete random control study.SETTING and MATERIALS: Study was completed in the Pharmaceutical Institute of Anhui Province. Materials included SD rats, 6-OHDA, apomorphine,rabbit-anti-TH serum, SR-6N rat cerebral solid orientation apparatus, etc.INTERVENTIONS: 6-OHDA was solidly and directionally injected into left SN area and corpus striatum pathway in SN in 90 SD rats to observe the changes in the behaviours and dopaminergic neuron morphology.MAIN OUTCOME MEASURES: Rotation behaviour, tremor and other abnormal behaviours, immunohistochemical observation, and electronic microscope observation.RESULTS: Sixty-four successful rat models(71% ) were screened by the induction of apomorphine. It was found from immunohistochemical observation that NDN in the injection side in SN signiftcantly reduced than that of the opposite side. It was found under electronic microscope that apoptosis and necrosis changes widely existed.CONCLUSION: This method is an effective method in the establishment of PD rat model, which has many similar aspects in behaviour and neuron morphology compared with PD patients.