帕金森病小鼠模型纹状体多巴胺转运蛋白^(125)I-β-CIT的放射自显影

^(125)I-β-CIT imaging study of striatal dopamine transporters in mice model of Parkinsonism

目的 观察不同损毁程度帕金森病 (PD)小鼠模型的纹状体多巴胺转运蛋白 (DAT)功能变化 ,探讨12 5I 甲基 3β (4 碘苯基 )托烷 2 β 羧酸盐 (β CIT)DAT显像的价值。 方法 根据注射MPTP天数不同 ,分为 1,3,5和 7d模型组和对照组 ,静脉注射12 5I β CIT 148kBq 2h后行放射自显影。高效液相色谱 电化学法 (HPLC ECD)检测纹状体多巴胺 (DA)及其代谢产物含量。免疫组化酪氨酸羟化酶 (TH)染色观察黑质和纹状体的病理变化。结果 与对照组相比 ,MPTP损毁的各组PD小鼠模型的纹状体 /皮层放射性比值分别降低 2 0 % ,42 % ,45 %和 5 2 % ;纹状体DA含量分别降低 47% ,75 % ,95 %和 95 % ;免疫组化TH染色可见黑质TH阳性神经元数量随MPTP损毁程度的加重而进一步减少。结论 不同损毁程度的PD小鼠模型DAT功能变化与生化和病理改变相一致 ,β

Objective To detect the activity of striatal dopamine transporters (DAT) in lesions of different order of severity of MPTP-induced mice model of parkinsonism by autoradiography with 125I-β-CIT and to evaluate the clinical use of the β-CIT imaging for DAT detection. Methods With regard to the different duration (days) of MPTP treatment, the C57BL mice were randomly divided into 5 groups, that is MPTP 1,3,5 and 7day groups and control group treated with normal saline instead of MPTP. Two hours after intravenous administration with 125I-β-CIT of 148 kBq, the brain tissue sections were imaged by autoradiography. The levels of dopamine (DA) and its metabolites were measured by high performance liquid chromatography and electrochemical detection (HPLC-ECD). The tyrosine hydroxylase (TH)-positive cells and fibres in the substantia nigra and striatum of the mice were observed by means of immunohistochemical technique. Results As compared with control group, the radioactivity ratios of striatum to cortex (ST/CX) in 4 MPTP-treated groups were significantly reduced,by 20%, 42%, 45% and 52%,respectively. The concentrations of DA in the striatum of 4 MPTP-treated groups were remarkably decreased,by 47%, 75%, 95% and 95%,respectively. The gradual loss of DA neurons and fibres in the substantia nigra and striatum in 4 MPTP-treated groups was observed under microscopy. Conclusions The functional abnormality of DAT paralleled the changes observed in neurochemistry and neuropathology studies in the lesions of different order of injury of the MPTP-treated mice. The β-CIT scanning for the activity of DAT may be useful for diagnosing PD at earlier phase and for monitoring the progression of the disease.