首都医科大学学报 ›› 2009, Vol. 30 ›› Issue (5): 611-615.doi: 10.3969/j.issn.1006-7795.2009.05.009

• PD的发病机制与早期诊断 • 上一篇    下一篇

共聚物-1致敏T淋巴细胞保护MPTP帕金森病模型小鼠黑质多巴胺能神经元

徐胜利, 宣琪, 周明   

  1. 首都医科大学宣武医院老年病研究所神经生物学研究室,神经变性病教育部重点实验室
  • 收稿日期:2009-07-16 修回日期:1900-01-01 出版日期:2009-10-21 发布日期:2009-10-21
  • 通讯作者: 徐胜利

T Lymphocytes from Copolymer-1 Immunized Mice Protect Dopaminergic Neurons in the MPTP Mouse Model of Parkinson's Disease

XU Sheng-li, XUAN Qi, ZHOU Ming   

  1. Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education
  • Received:2009-07-16 Revised:1900-01-01 Online:2009-10-21 Published:2009-10-21

摘要: 目的 明确C57BL/6J小鼠MPTP模型保护黑质多巴胺(dopamine,DA)神经元的共聚物-1(Copolymer-1,Cop-1)致敏淋巴细胞的类型。方法 将80只雄性C57BL/6J小鼠分为Cop-1/BSA致敏淋巴细胞移植组、Cop-1/BSA致敏T淋巴细胞移植组、去T淋巴细胞Cop-1/BSA致敏淋巴细胞移植组、MPTP模型组和正常对照组,每组10只。C57BL/6J小鼠1 d内接受4次MPTP(18 mg·kg-1)腹膜腔注射,每次注射间隔2 h,正常对照组动物仅接受等量的0.9%氯化钠注射液注射。MPTP末次注射后,除MPTP模型组和正常对照组动物外,其他组动物立即分别接受不同的Cop-1/BSA致敏淋巴细胞移植。细胞移植7 d后处死动物,取脑。酪氨酸羟化酶免疫组化及体视学方法定量分析黑质DA神经元数。结果 黑质DA神经元定量分析显示,MPTP注射使模型对照组黑质DA神经元减少到正常对照组的37.68%,BSA致敏淋巴细胞移植组(38.15%)、BSA致敏T淋巴细胞移植组(41.44%)和去T淋巴细胞的Cop-1/BSA致敏淋巴细胞移植组结果(Cop-1:40.06%,BSA:34.81%)和模型对照组类似。而Cop-1致敏淋巴细胞移植和Cop-1致敏T淋巴细胞移植组黑质DA神经元数为正常对照组的74.38%和84.64%,DA神经元数明显高于模型对照组、BSA致敏淋巴细胞移植组和去除T淋巴细胞的BSA/Cop-1致敏淋巴细胞移植组(P<0.01)。结论 在MPTP C57BL/6J小鼠模型,Cop-1致敏T淋巴细胞可有效对抗MPTP毒性,保护黑质DA神经元。

关键词: 帕金森病, 共聚物-1, T淋巴细胞

Abstract: Objective To define the phenotype of Copolymer-1(Cop-1) antigen-specific lymphocytes to protect the dopaminergic neurons in 1-methy1-4-pheny1-1,2,3,6-tetrahydropyritine(MPTP)-intoxicated C57BL/6J mice. Methods The C57BL/6J mice were divided randomly into Cop-1/BSA antigen-specific lymphocyte adoptive transfer, Cop-1/BSA antigen-specific T lymphocyte adoptive transfer, Cop-1/BSA antigen-specific lymphocyte without T cells adoptive transfer, MPTP model control and normal control groups. All the mice except normal controls received four intraperitoneal injections at 2 hour intervals of MPTP(18 mg·kg-1). After the last injection, the animals of transfer groups received adoptive transfers of different types of antigen-specific lymphocytes immediately. All mice were killed after 7 days of last MPTP injection. The dopaminergic neurons were analyzed quantitatively using immunohistochemistry of tyrosine hydroxylase(TH) and stereological counts. Results Stereological counts revealed that that MPTP caused a significant loss of TH-positive neurons in substantia nigra(SN) (37.78% of normal controls). Similar results were observed in MPTP-injected mice that received BSA-lymphocytes(38.15% of normal controls), BSA-T-lymphocytes(41.44% of normal controls), Cop-1/BSA lymphocytes without T cells transfer(Cop-1: 40.06% of normal controls; BSA: 34.81% of normal controls). In contrast, MPTP-injected mice that received Cop-1 lymphocytes or Cop-1-T-lymphocytes exhibited a much smaller reduction in the number of TH-positive neurons(74.38%, or 84.64% of normal controls). Conclusion Cop-1 antigen-specific T lymphocytes may protect dopaminergic neurons in SN of MPTP C57BL/6J mouse.

Key words: Parkinson’s disease, Copolymer-1, T lymphocyte

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