小鼠帕金森病模型多巴胺转运体、脑血流灌注与葡萄糖代谢变化

Striatal dopamine transporter, regional cerebral blood flow and glucose utilization in MPTP-induced Parkinson disease mice model

目的联合观察不同剂量1甲基4苯基1,2,3,6四氢吡啶(MPTP)对小鼠多巴胺神经系统、局部脑血流灌注和葡萄糖代谢的损伤效应。方法8周龄雄性C57BL6小鼠,按体重腹腔注射0～80mgkg的MPTP,10d后用免疫组织化学法测定黑质酪氨酸羟化酶(TH)阳性细胞数,放射自显影法测定尾壳核多巴胺转运体(DAT)相对含量、尾壳核和丘脑局部血流量与葡萄糖代谢水平。结果随MPTP用量增加,DAT损耗和TH阳性细胞数减少程度均加重,两者呈正相关(r=0.998,P<0.05)。其中80mgkg组平均DAT损耗达79.8%(P<0.001),TH阳性细胞数减少达54.1%(P<0.001)。尾壳核和丘脑局部血流量在各组之间差异无显著性(P>0.2)。尾壳核、丘脑葡萄糖代谢在80mgkg组分别下降了3.0%和5.4%(P<0.05)。结论MPTP引起黑质多巴胺神经元和尾壳核DAT丧失存在明显剂量效应关系,尾壳核和丘脑的局部血流灌注变化不明显,葡萄糖代谢在高剂量组有轻微下降。

Objective To explore the variation of regional cerebral blood flow (rCBF), glucose utilization as well as the neurotoxic effect on dopaminergic neurons induced by neurotoxin 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods Eight-week old male C57BL/6 mice were given a total dose of 0～80 mg/kg MPTP intraperitoneally. Ten days later the mice were sacrificed for tyrosine hydroxylase (TH)-immunopositive cell counting in substantia nigra using SP immunohistochemistry. Vivo autoradiography was employed to measure striatal dopamine transporter (DAT) loss, rCBF and glucose utilization in striatum and thalamus. Results The extents of DAT depletion and TH-immunopositive cell loss were positively correlated (r=0.998, P<0.05) in a dose-dependent manner with a high DTA loss reached 79.8% (P<0.001) and decreasing TH positive cell to 54.1% (P<0.001) noted in 80 mg/kg MPTP-treated group. There were no statistical differences in rCBF in striatum and thalamus among different groups (P>0.2), while glucose utilization was only slightly reduced in caudate/putamen and thalamus by 3.0% and 5.4% in 80 mg/kg MPTP-treated mice (P<0.05). Conclusion Significant dose-dependent relationship was in presence of MPTP induced dopaminergic neurons loss, changes of rCBF in caudate/putamen and thalamus were not significant, while the glucose utilization was slightly decreased in higher dose group.