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稳定表达GDNF的MN9D/GDNF工程细胞可明显改善帕金森病模型大鼠的旋转行为

GDNF engineered MN9D cells can improve the rotational behavior on a rat model of Parkinson disease

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【作者】 经兴军马端端高红王晓民韩济生

【Author】 JING Xing Jun, MA Duan Duan, GAO Hong, WANG Xiao Min, HAN Ji Sheng (Neuroscience Research Institute, Beijing Medical University, Beijing 100083)

【机构】 北京医科大学神经科学研究所

【摘要】 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。

【Abstract】 Objective: To observe whether engineered MN9D/GDNF cells stably expressing GDNF and secreting dopamine can improve the APO induced rotational behavior on a rat model of Parkinson disease. Methods: By mircroinjecting 6 OHDA into rat unilateral medial forebrain bundle to induce the damage of unilateral mesencephalic dopamine neurons, a well known PD rat model was established. After transplanting MN9D/GDNF engineered cells into the lesioned striatum by stereotaxic technique, the rotational behavior was measured on an automatic locomoter. Results: Engineered MN9D/GDNF cells steadily expressing GDNF could significantly reduce the rotational behavior of PD rat model for ten weeks. Conclusion: Combination of prevention and treatment for PD by ex vivo method may play an important role in the basic research and clinical utility of gene therapy on Parkinson disease in the future.

【基金】 家自然科学基金,跨世纪优秀人材国家“九·五”攻关(969060508)资助
  • 【文献出处】 北京医科大学学报 ,JOURNAL OF BEIJING MEDICAL UNIVERSITY , 编辑部邮箱 ,1999年03期
  • 【分类号】R742.5
  • 【被引频次】2
  • 【下载频次】90
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