共聚物-1对帕金森病模型小鼠多巴胺能神经元的保护作用

目的探讨共聚物-1(Cop-1)免疫或致敏淋巴细胞移植对帕金森病模型小鼠黑质多巴胺(DA)神经元的保护作用。方法选用雄性C57BL/6J小鼠随机分为Cop-1/BSA免疫组、Cop-1/BSA致敏淋巴细胞移植组、MPTP模型组和正常对照组。Cop-1/BSA免疫组在注射MPTP之前10天接受Cop-1/BSA抗原免疫;Cop-1/BSA致敏淋巴细胞移植组动物在MPTP末次注射后,立即接受Cop-1/BSA致敏淋巴细胞移植;MPTP模型组动物仅接受MPTP注射;正常对照组动物仅接受生理盐水注射。MPTP末次注射7天后处死动物,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 MPTP注射显著地减少了模型动物黑质DA神经元数量。Cop-1免疫和Cop-1致敏淋巴细胞移植明显增加了MPTP模型动物黑质DA神经元数,对黑质DA神经元有保护作用。BSA免疫或BSA致敏淋巴细胞移植则没有表现出这种保护作用。结论在C57BL/6J小鼠,Cop-1免疫和Cop-1致敏淋巴细胞移植可有效对抗MPTP毒性,保护黑质DA神经元。

Copolymer-1 protection on the dopaminergic neurons of the model of Parkinson's disease in mice

Objective To explore the dopaminergic neuroprotection of Copolymer-1（Cop-1）immunity or adoptive transfer of Cop-1 specific lymphocytes in MPTP-intoxicated C57BL/6J mice.Methods The C57BL/6J mice were divided randomly into Cop-1/BSA immunity,Cop-1/BSA antigen-specific lymphocyte adoptive transfer,MPTP model control and normal control groups.The animals of immunized groups were immunized with Cop-1 or BSA 10 days before MPTP injection.The mice except normal control group received four i.p.injections at 2 hour intervals of MPTP（18mg kg-1）.After the last injection,the animals of transfer group received adoptive transfers of two antigen-specific lymphocytes immediately.All mice were killed after 7 days of last MPTP injection.The dopaminergic neurons were analyzed quantitatively using immunohistocheministry of tyrosine hydroxylase（TH）and stereological counts.Results Stereological counts revealed that MPTP caused 58.02% loss of TH-positive neurons in substantia nigra（SN）compared with saline controls.Similar results were observed in MPTP-injected mice that received BSA immunity or lymphocytes from BSA-immune donors.In contrast,MPTP-injected mice that received Cop-1 immunity or Cop-1 specific lymphocytes exhibited a much smaller reduction in the number of TH-positive neurons compared with MPTP or MPTP/BSA animals.Conclusion It is suggested that Cop-1 immunity or Cop-1 specific lymphocytes transfer may have a neuroprotective effect and provide benefits for Parkinson＇s disease.