【摘要】 背景:应用6-羟基多巴胺(6-Hydroxydopamine,6-OHDA)损毁黑质多巴胺神经元(nigraldopaminergicneuron,NDN)制作的大鼠模型,在目前帕金森病的研究中应用最广,但由于黑质致密部体积狭小,技术难度大,故模型制备成功率一般仅为30%～40%左右。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,并对模型进行评价。设计:完全随机的实验研究。地点和材料:实验在安徽中医学院第一附属医院中心实验室完成,实验材料包括SD大鼠,6-OHDA,阿朴吗啡,兔抗TH血清,ABC试剂盒,SR-6N大鼠脑立体定向仪,JEM-100CX电镜。干预:取SD大鼠90只,将6-OHDA立体定向微量注射于左侧黑质区及黑质纹状体通路,观察大鼠行为及黑质细胞形态学变化。主要观察指标:旋转行为,免疫组织化学观察多巴胺能神经元数量,电镜观察多巴胺能神经元形态改变。结果:90只大鼠中经阿朴吗啡诱导后有64只(占71%)恒定转向右侧且结果稳定,旋转圈数30min>210r,被视为成功大鼠模型;免疫组化观察发现注射侧黑质区多巴胺能神经元较对侧明显减少,电镜观察发现其普遍存在凋亡及坏死样改变。结论:应用本方法可较快建立稳定的成功率较高的大鼠模型,但在病理和行为学等方面同自然患者仍有较多差异。更多还原

【Abstract】 BACKGROUND: The most commonly used animal model of Parkinson’s disease is cre ated by lesion of nigral dopaminergic neuron (NDN) resulted from intrastriatial injection of 6-hydroxydopamine (6-OHDA). However, the success rate is as low as 30%-40% because of the tiny size of the striate. OBJECTIVES: To investigate the feasibility of a new method using 6-OHDA to create Parkinson model in rats with a higher success rate. DESIGN:Full-randomized experimental study. SETTING AND MATERIALS:The experiment was finished in the Central Laboratory,t he First Affiliated Hospital of Anhui College of Traditional Chinese Medicine. S D rats,6-OHDA,Apomorphine,rabbit anti-TH serum,ABC kit,SR-6N stereotaxic i nstrument and JEM-100CX electron microscope. INTERVENTION:Ninety SD rats received left side intrastriatal stereotaxic inje ction of 6-OHDA. Behavioral analysis of turning and morphological analyses on quantity and structure of doparminergic neurons(DN) were performed. MAIN OUTCOME MEASURES:Rotation behavior,the number of dopaminergic neurons by immunohistochemistry,and the neurological changes of dopaminergic neurons by el ectron microscope. RESULTS: A success Parkinson model was considered when the level of turning i nduced by apomorphine above 210 turns per 30 minutes. The success rate was 71% (Parkinson model in 64 out of 90 rats). Immunohistochemistry revealed decreased number of DNs in the injection side than that in the contralateral side. Electro n microscopy(EM) found apoptosis and necrosis in the injection area. CONCLUSIONS: This new method is able to create reliable Parkinson’s disease m odel in rats in a high success rate, although the pathology and behaviour of Par kinson rats differ somehow from those of natural Parkinson’s disease.更多还原