中国药物警戒 ›› 2021, Vol. 18 ›› Issue (4): 312-314.
DOI: 10.19803/j.1672-8629.2021.04.03

• 帕金森病药物研究模型专栏 • 上一篇    下一篇

A53T转基因小鼠体内α-突触核蛋白改变研究

韩奇文, 温路, 陈乃宏, 苑玉和*   

  1. 中国医学科学院北京协和医学院药物研究所,北京 100050
  • 收稿日期:2020-12-14 出版日期:2021-04-15 发布日期:2021-04-23
  • 通讯作者: *苑玉和,女,博士,研究员·博导,神经药理学和抗帕金森病创新药物研制及作用机制研究。E-mail：yuanyuhe@imm.ac.cn
  • 作者简介:韩奇文,女,硕士,神经药理学。
  • 基金资助:
    国家自然科学基金项目（81773925）; 北京市自然基金（7212156）

Changes of α-Synuclein in A53T Transgenic Mice

HAN Qiwen, WEN Lu, CHEN Naihong, YUAN Yuhe*   

  1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • Received:2020-12-14 Online:2021-04-15 Published:2021-04-23

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摘要： 目的 研究α-突触核蛋白 （α-synuclein, α-syn） A53T转基因小鼠体内α-syn的分布和修饰变化情况。方法 采用α-syn A53T转基因小鼠作为帕金森病（parkinson's disease, PD）模型小鼠,应用Western blot实验方法来检测A53T转基因小鼠和野生型C57BL/6小鼠的胃、黑质和纹状体中α-syn的表达含量和异常聚集情况。结果 相比于野生型小鼠,A53T转基因小鼠的胃、黑质和纹状体中α-syn（C-20）、硝基化α-syn（n-syn）表达均显著增加;胃和黑质中的磷酸化α-syn（p-syn）含量降低,纹状体中p-syn含量升高;黑质和纹状体中寡聚体形式的α-syn（5G4）含量升高,胃中含量降低。其中,n-syn在胃组织中含量最高,寡聚体形式的α-syn在黑质部位含量最高,p-syn在纹状体部位含量最高。结论 A53T转基因小鼠体内α-syn总蛋白增加,而异常修饰和聚集化的α-syn在不同器官内的含量变化有所差异,提示A53T相关的α-syn病变有组织特异性分布特点。

关键词: 帕金森病, A53T转基因小鼠, α-突触核蛋白, 异常形式

Abstract: Objective To study the distribution and modification of α-synuclein (α-syn) in α-synuclein A53T transgenic mice. Methods The α-syn A53T transgenic mice were used as Parkinson's disease (PD) model mice. Western blot was used to detect the expression and abnormal aggregation of α-syn in the stomach, substantia nigra and striatum of A53T transgenic mice and wild-type C57BL/6 mice. Results Compared with wild-type mice, the expressions of total α-syn (C-20) and nitrosylated α-syn (n-syn) in the stomach, substantia nigra and striatum of A53T transgenic mice increased. The content of phosphorylated α-syn (p-syn) in the stomach and substantia nigra decreased, while the content of p-syn in the striatum increased. The content of α-syn (5G4) in the form of oligomers in the substantia nigra and striatum increased, but decreased in the stomach. Among them, n-syn had the highest content in stomach tissues, α-syn in the form of oligomers had the highest content in the substantia nigra, and p-syn had the highest content in the striatum. Conclusion The total α-syn protein in A53T transgenic mice increases, and the content of abnormally modified and aggregated α-syn varies in different organs, suggesting that the pathological changes of the organs are specific in the pathogenesis of PD.

Key words: Parkinson's disease, A53T transgenic mice, α-synuclein (α-syn), abnormal form

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