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目的:观察稳定表达GDNF的MN9D/GDNF工程细胞对6羟基多巴胺损毁所致帕金森病(Parkinsondisease,PD)模型大鼠旋转行为有无治疗作用。方法:用6羟基多巴胺损毁大鼠单侧中脑黑质多巴胺能神经元、2周后腹腔注射阿朴吗啡诱导大鼠出现偏侧旋转行为的方法制备PD模型大鼠。通过脑立体定位技术,将稳定表达GDNF的MN9D/GDNF工程细胞注入模型鼠损毁侧纹状体,1周后观察阿朴吗啡诱导的旋转行为有无改善。结果:稳定表达GDNF的MN9D/GDNF工程细胞可明显降低PD模型大鼠的异常旋转行为,治疗作用达10周之久。结论:运用exvivo方法和防治兼顾的策略对于PD基因治疗的基础研究及临床应用具有重要意义。
OBJECTIVE: To investigate the effect of MN9D / GDNF engineered cells stably expressing GDNF on the rotational behavior of rats with Parkinson’s disease (PD) induced by 6-hydroxydopamine damage. Methods: PD model rats were prepared by destroying dopaminergic neurons in substantia nigra of rats with 6hydroxy dopamine and apomorphineinduced rats by intraperitoneal injection after 2 weeks. Through the brain stereotaxic technique, MN9D / GDNF engineered cells stably expressing GDNF were injected into the striatum of the model rats to destroy the striatum. After 1 week, apomorphine-induced rotation behavior was observed. Results: MN9D / GDNF engineered cells stably expressing GDNF could significantly reduce the abnormal rotation behavior of rats with PD model for up to 10 weeks. Conclusion: The exvivo method and the strategy of both prevention and treatment are of great significance for the basic research and clinical application of PD gene therapy.