The basic study for the therapy of spinal damages by immuno-related cells and/or immuno suppression drug thorough the production of neurotrophic factors.

FK 506是一种免疫抑制剂，近年来有研究报道其对中枢神经系统神经元变性有保护作用，但其作用机制尚未完全阐明。本研究探讨了FK 506对胶质细胞源性神经营养因子（GDNF）诱导的影响，以及GDNF对多巴胺能神经元变性的保护作用。从胚胎大鼠海马培养的神经元在FK 506的存在下培养，并评估神经元细胞存活和培养基中GDNF的浓度。采用特异性和敏感性双抗体夹心酶免疫分析法（EIA）测定GDNF的含量。在体内研究中，FK 506（1.5 mg/kg）腹腔注射给药至小鼠，伴或不伴纹状体注射6-OHDA。采用EIA法和甲基非他明诱导的旋转行为法分别检测各组大鼠脑内GDNF含量和纹状体神经元变性程度，结果表明：FK 506可剂量依赖性地增加神经元条件培养液中GDNF含量。FK 506同时保护培养的神经元免于细胞死亡。此外，外周给药FK 506增加了小鼠纹状体中GDNF的含量。FK 506可减少纹状体损伤小鼠由metanphetamin诱导的旋转次数。结论：1）FK 506通过诱导GDNF的表达，对多巴胺能神经元的变性具有保护作用。2)免疫抑制剂如FK 506可能成为治疗帕金森病的新药物。

FK506, one of the immunosuppressant drugs, has been recently reported to protect neuronal degeneration in the central nervous system, however, the mechanisms of action were not completely clarified. In this study, we investigated the effects of FK506 on the induction of glial cell line-derived neurotrophic factor (GDNF), and involvement of the induced GDNF in the protection against degeneration of dopaminergic neurons. Neurons cultured from embryonic rat hippocampus were cultured in the presence of FK506, and neuronal cell survival and concentration of GDNF in the medium were assessed. GDNF was measured by the specific and sensitive enzyme immunoassay (EIA). In vivo study, FK506 (1.5 mg/kg) was intraperitoneally administrated to mice with or without striatal injection of 6-OHDA. The content of GDNF in the various brain regions, and the degree of neuronal degeneration of striatum were then estimated by the EIA and their rotation behavior induced by methanphetamine, respectively.FK506 elevated GDNF contents in the media conditioned with neurons in dose-dependent manners. FK506 simultaneously protected cultured neurons from the cell death. Further, peripheral administration of FK506 increased GDNF contents in the striatum of mice. The number of rotation induced by metanphetamin was reduced by the administration of FK506 in striatum lesioned mice. The increase of GDNF content and suppression of the number of rotation were well-correlated each other, suggesting protective effects of it on dopaminergic neurons.In Conclusions, 1) FK506 protects dopaminegic degeneration through induction of GDNF in vivo and in virto. 2) Immnonosapressive drugs such as FK506 may be a candidate for a novel therapeutic agent for Parkinson's disease.