中文摘要：

目的：明确在C57BL／6小鼠纹状体过表达野生型的人源帕金森相关蛋白PINKl能否减轻由侧脑室注射鱼藤酮引起多巴胺神经元损伤。方法：通过向C57BL／6小鼠（雄性，7周龄，18～20g）左侧纹状体中注射带有GFP人源野生型PINKl及突变体PINKl∞㈣的慢病毒包装颗粒，两周后向小鼠左侧侧脑室中定位注射鱼藤酮，通过蛋白质印迹，免疫组化和行为学的方法检测PINKl对鱼藤酮引起多巴胺神经元损伤的影响。结果：蛋白质印迹和免疫组化的实验都证明了在C57BL／6小鼠纹状体过表达野生型的PINKl对于鱼藤酮引起多巴胺能神经元的减少有明显的抑制作用（P〈0．01），但对鱼藤酮引起的行为学损伤没有明显的改善作用。

英文摘要：

Background ： The etiology of Parkinson ＇ s disease （ PD ） involves genetic, environmental, endogenous neurotoxins and other factors. But the current weight of evidence strongly suggests that environmental neurotoxins may play an important role in the etiology of PD. Rotenone is a classical mitochondrial complex-I inhibitor and is the most potent member of the rotenoids, a family of isoflavonoids extracted from Leguminosae plants. More recently, chronic intraperitoneal injection of rotenone has been shown to cause dosedependent dopamine （DA） loss, reduced tyrosine hydroxylase （TH） immunoreactivity, and behavioral abnormalities in rats. WEN-induced kinase 1 （PINK1） is linked to recessive PD. Pink1 deletion results in impaired DA release and decreased mitochondrial respiration in the striatum of mice. Objective ： To test if overexpression of PINK1 in C57BL/6 mice striatum may alleviate the injury of dopaminergic neuron caused by Rotenone. Methods： Lentivirns of GFP-PINK1-LV, GFP-PINK1G3~gD-LV or GFP-vector-LV were injected into the C57BL/6 mice （male, 7 weeks old,18-20g weight） striatum. Two weeks later, Rotenone dissolved in DMSO was injected into the C57BL/6 mice lateral ventricles. After 2 weeks, TH protein level in C57BL/6 mice striatum was measured by Western blotting and Immunohistochemieal staining. Meanwhile the behavioral performance was evaluated in Open Filed experment. Results： Western blotting and immunohistochemical experiments have proved that over- expression of wild-type PINK1 in C57BL/6 mice striatum may rescue the TH protein level reduction, but can not alleviate the behavioral injury caused by Rotenone.