论文部分内容阅读
背景:目前,铁代谢障碍已被公认为帕金森发病的一个关键因素,但是脑铁代谢的研究仍处于起步阶段,胶质细胞在脑铁代谢中所扮演的角色还不清楚。许多研究显示,小胶质细胞在帕金森发病中起重要的作用,且与铁的关系密切。目的:在前期研究的基础上,深入探讨小胶质细胞与神经元在铁代谢领域的关系,阐明小胶质细胞在铁选择性损伤多巴胺能神经元致帕金森中的作用。方法:实验为体外细胞学实验,在中国山东,青岛大学医学院完成。(1)改变小胶质细胞铁的水平,观察小胶质细胞条件培养基对中脑神经元的存活率及铁代谢的影响。用脂多糖激活不同铁水平的小胶质细胞,观察小胶质细胞条件培养基对中脑神经元存活率及铁代谢的影响;(2)应用小干涉RNA、ELASA方法观察小胶质细胞内不同的铁水平对小胶质细胞及其激活时所释放的炎症因子和乳铁蛋白的影响,观察小胶质细胞释放的炎症因子和乳铁蛋白对神经元存活率及铁代谢的影响;(3)改变中脑神经元的铁水平,然后加入上述小胶质细胞条件培养基,观察中脑神经元存活率及铁代谢的变化。实验方案经医院伦理委员会批准,批准号为01482 311234。大鼠的实验操作和取材遵循《关于善待实验动物的指导性意见》规定,并与美国国立卫生与健康研究院的指南一致。结果与结论:实验证实了小胶质细胞的功能与黑质多巴胺能神经元铁代谢密切相关,如何调控小胶质细胞的功能使其向保护神经元的方向发展,这一方面的研究进展无疑将对帕金森病的防治有极大的推动作用。
BACKGROUND: Currently, iron metabolism disorders have been recognized as a key factor in the pathogenesis of Parkinson’s disease. However, the study of brain iron metabolism is still in its infancy. The role of glial cells in brain iron metabolism is unclear. Numerous studies have shown that microglia play an important role in the pathogenesis of Parkinson’s disease and are closely related to iron. OBJECTIVE: On the basis of previous studies, the relationship between microglia and neurons in iron metabolism was further investigated and the role of microglia in Parkinson’s disease induced by iron selective damage to dopaminergic neurons was elucidated. Methods: The experiment was an in vitro cytology experiment, which was completed in Shandong University and Qingdao University Medical College. (1) To change the level of iron in microglia, observe the effect of microglia conditioned medium on the survival rate of midbrain neurons and iron metabolism. Lipopolysaccharide (LPS) was used to activate microglia cells with different iron levels to observe the effect of microglia conditioned medium on the survival rate and iron metabolism of midbrain neurons. (2) Small interfering RNA and ELASA were used to observe the effect of microglia Effects of different iron levels on the release of inflammatory factors and lactoferrin in microglial cells and their activation, and the effects of inflammatory factors released by microglia and lactoferrin on neuronal viability and iron metabolism; 3) Change the iron level of the midbrain neurons, then add the above microglia conditioned media to observe the changes of the midbrain neuron survival and iron metabolism. The experimental protocol was approved by the hospital ethics committee with the approval number of 01482 311234. Experimental procedures and accessions to rats are governed by the Guidance on Good Laboratory Animal Care and are consistent with the guidelines of the National Institute of Health and Human Services. RESULTS AND CONCLUSION: The experiment confirmed that the function of microglia is closely related to the iron metabolism of dopaminergic neurons in substantia nigra, and how to regulate the function of microglia to protect the neurons is undoubtedly the research progress. Parkinson’s disease prevention and treatment will have a great role in promoting.