脂多糖加重α-synuclein基因突变小鼠多巴胺能神经元损伤机制的研究

发布时间：2018-06-29 14:14

本文选题：帕金森氏病 + 脂多糖　；参考：《药学学报》2017年05期

【摘要】：帕金森氏病(Parkinson’s disease,PD)是由遗传和炎症等多种病因引起的神经退行性疾病。有多种可模拟PD发病的动物模型,α-synuclein(A53T)转基因小鼠和脂多糖(lipopolysaccharide,LPS)腹腔注射小鼠分别从基因突变和炎症角度模拟PD的病理改变,但这些模型仅模拟PD发病的单一因素,且出现病理改变的时间较长。本实验采用LPS注射α-synuclein转基因小鼠建立炎症和遗传因素双重打击的PD模型。结果显示LPS联合α-synuclein转基因刺激可明显引起小鼠运动协调能力和多巴胺神经元功能障碍,以上行为学和病理改变均较二者单独刺激明显加重,表现出协同效应。机制研究发现LPS联合α-synuclein可引起明显的神经炎症和神经元凋亡,差异蛋白质组学研究发现LPS和α-synuclein双重打击可导致小鼠脑中与炎症和凋亡相关蛋白CD99抗原样蛋白2(CD99L2)和细胞色素C氧化酶7A相关蛋白(COX7RP)的表达明显提高,提示这两种蛋白可能参与PD的发病过程。以上研究表明在基因突变基础上引入炎症刺激可建立更理想的PD动物模型。
[Abstract]:Parkinson's disease (PD) is a neurodegenerative disease caused by heredity and inflammation. There are many animal models that can simulate the pathogenesis of PD. 伪 -synuclein (A53T) transgenic mice and lipopolysaccharide LPS (LPS) mice are injected intraperitoneally to simulate the pathological changes of PD from the perspective of gene mutation and inflammation respectively, but these models only mimic the single factor of PD. The pathological changes occurred for a long time. In this study, LPS injection of 伪 -synuclein transgenic mice was used to establish a PD model with both inflammatory and genetic factors. The results showed that LPS combined with 伪 -synuclein transgenic stimulation could significantly induce motor coordination and dopamine neuron dysfunction in mice, and the behavioral and pathological changes were significantly more severe than those of the two stimuli alone, showing synergistic effect. It was found that LPS combined with 伪 -synuclein could induce obvious neuritis and neuronal apoptosis. Differential proteomics studies showed that LPS and 伪 -synuclein could significantly increase the expression of CD99 antigen-like protein 2 (CD99L2) and cytochrome C oxidase 7A-associated protein (COX7RP) in mouse brain. These two proteins may be involved in the pathogenesis of PD. These studies suggest that the introduction of inflammatory stimulation on the basis of gene mutation can establish a more ideal animal model of PD.
【作者单位】：中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室;
【基金】：国家自然科学基金资助项目(81630097) 中国医学科学院医学与健康科技创新工程资助项目(2016-I2M-3-011)
【分类号】：R742.5

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