MPTP小鼠脑沉默信息调节因子1和缺氧诱导因子-1α的表达及行为学检测

发布时间：2018-07-09 09:52

本文选题：帕金森病 + 沉默信息调节因子　；参考：《国际神经病学神经外科学杂志》2017年01期

【摘要】：目的本研究旨在研究MPTP模型小鼠中沉默信息调节因子1(SIRT1)和缺氧诱导因子1α(HIF-1α)的表达情况以及行为学的变化。方法选用MPTP处理C57BL/6小鼠构建PD动物模型,采用行为学实验、高效液相色谱(HPLC)、免疫组化等方法检验模型的建立是否成功,并在小鼠模型中检测SIRT1和HIF-1α的表达情况。结果 MPTP处理的小鼠表现出显著的行为学异常,主要体现在自主活动减少(P0.001)、步距缩短(P0.001),且有显著运动迟缓(P0.001)。HPLC结果发现,模型组小鼠纹状体区域多巴胺(DA)及其代谢产物减少(P0.001)。免疫组化结果提示黑质区域多巴胺能神经元标志物酪氨酸羟化酶(TH)和多巴胺转运体(DAT)的表达明显下调(P0.01)。分子生物学方面,PD模型小鼠的SIRT1表达降低(P0.05),HIF-1α表达增加(P0.05)。结论 PD模型小鼠表现出明显的行为学异常,多巴胺能神经元标志物检测提示成功复制PD动物模型,同时发现模型小鼠的SIRT1/HIF-1α的表达异常,提示该信号通路可能参与了PD的疾病过程。
[Abstract]:Objective to investigate the expression of silencing information regulatory factor 1 (SIRT1) and hypoxia inducible factor-1 伪 (HIF-1 伪) in MPTP model mice and the changes in behavior. Methods MPTP was used to treat C57BL / 6 mice to construct PD animal model. Behavioral experiment, high performance liquid chromatography (HPLC) and immunohistochemistry were used to test the success of the model. The expression of SIRT1 and HIF-1 伪 was detected in mouse model. Results MPTP treated mice showed significant behavioral abnormalities, mainly reflected in decreased autonomous activity (P0.001), shorter step distance (P0.001), and significant motor retardation (P0.001). HPLC results showed that dopamine (DA) and its metabolites (P0.001) in the striatum region of the model group were decreased (P0.001). The immunohistochemical results showed that the expression of tyrosine hydroxylase (th) and dopamine transporter (DAT) in dopaminergic neurons in substantia nigra was down-regulated (P0.01). In molecular biology, the expression of SIRT1 decreased (P0.05) and the expression of HIF-1 伪 increased (P0.05). Conclusion PD model mice showed obvious behavioral abnormalities. The detection of dopaminergic neuron markers suggested that PD animal models were successfully reproduced, and the abnormal expression of SIRT1 / HIF-1 伪 was also found in the model mice. This signal pathway may be involved in the disease process of PD.
【作者单位】：上海交通大学附属第一人民医院神经内科;新乡医学院第三附属医院神经内科;上海交通大学药学院;
【基金】：国家自然科学基金(81371410;81671251) 上海交通大学医工交叉基金(YG2014MS31)
【分类号】：R742.5

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