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

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

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1d内接受4次MPTP(18mg.kg-1)腹膜腔注射,每次注射间隔2h,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7d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MPTPC57BL/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。

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.