50 mg-kg剂量左旋多巴对帕金森病大鼠神经行为学及超微结构影响.doc

50 mg/kg剂量左旋多巴对帕金森病大鼠神经行为学及超微结构影响 　 作者：何建成 王文武 丁宏娟 王慧 【摘要】 目的 观察50 mg/kg剂量左旋多巴(Ldopa)对帕金森病（PD）大鼠神经行为学和超微结构的影响。方法 采用脑部偏侧注射6羟基多巴胺（6OHDA）制备PD模型，进一步腹腔注射50 mg／kg剂量Ldopa，连续4 w。每周观察2次行为学〔异常不自主动作(AIM)评分、对侧旋转行为的评定〕，并进行阿扑吗啡（apomorphine，APO）诱导PD大鼠对侧旋转行为的评定。实验结束后行心脏灌注固定，分离双侧黑质、纹状体，进行透射电镜观察。结果 模型大鼠对APO诱导的旋转圈数、AIM评分、大鼠旋转启动时间，在2、3、4 w中，差异无统计学意义（P＞0.05）。旋转持续时间、药效期平均旋转圈数、剂峰旋转圈数，虽有增加的趋势，但仅与第3天比较，差异有统计学意义（Plt;0.05）。大鼠注射侧（右侧）黑质、纹状体出现细胞膜皱缩，细胞体积缩小，线粒体嵴部分溶解，细胞核皱缩或不规则，核膜部分不完整等。结论 50 mg/kg Ldopa对PD大鼠具有明显的神经毒性，有典型的神经行为学改变和超微结构改变。模型稳定，可用于后续研究。 【关键词】 左旋多巴；帕金森病；模型；神经行为学；超微结构 【Abstract】Objective To observe the effect of 50 mg/kg Ldihydroxyphenylalanine (Ldopa) on neuroethology and ultra microstructure of rats with Parkinson′s disease (PD). Methods The unilateral PD model was made by injecting 6OHDA/Benserazide into the right substantia nigra. The successful PD models were applied with 50 mg/kg Ldopa intraperitoneal injection for 4 w. Neuroethology was observed twice a week grading of abnormal involuntary movement(AIM) and evaluation of contralateral rotation] and the evaluation of contralateral rotation was done on rats with PD induced by apomorphine(APO). After experiment, perfusion fixation was used on rats and substantia nigra and corpus striatum were separated for a study of transmission electron microscopy. Results The circle count, the gradings of AIM and startup time of rotation at the time of 2, 3 and 4 w were not significantly different for the rats induced by APO（P＞0.05）. The duration of rotation, average circle count in pharmacological action and circle count of peak rotation had got the tendency of increase, but only on the 3rd day had significantly difference（Plt;0.05）.The substantia nigra and corpus striatum in the injected lateral (right side) were altered as evidenced by crenulated cell membrane, decreased cell volume, partly dissolved mitochondrial cristae, crenulated or irregular cell nuclear and incomplete nuclear membrane.Conclusions 50 mg/kg Ldopa has got obvio