颈内动脉注射MPTP制作偏侧恒河猴帕金森病模型研究

Experimental study on preparation of hemiparkinsonism rhesus monkey model by unilateral internal carotid artery infusion of MPTP

目的探讨经颈内动脉注射MPTP制作偏侧恒河猴帕金森病模型的稳定技术和方法。方法对10只健康恒河猴注射MPTP,其中5只行颈外动脉夹闭,颈总动脉注射;5只行颈总动脉穿刺插管颈内动脉给药。其中1只模型动物在造模前后行正电子发射断层显像(PET)检查,观察脑代谢改变情况。对模型动物脑标本行快速冷冻切片,采用免疫组织化学方法检测多巴胺能细胞变化。结果采用颈总动脉插管颈内动脉注药建模均一次成功;2只颈外动脉夹闭颈总动脉注射药物建模一次成功,不成功的3只采用颈总动脉插管至颈内动脉再次注入相同剂量MPTP后建模成功。PET显示模型侧基底核区低代谢,与术前相比明显不同。免疫组化检测示模型侧中脑黑质酪氨酸羟化酶(TH)阳性细胞形态改变,数量减少,与对照侧有明显差异。结论与颈外动脉夹闭颈总动脉注射相比,颈总动脉插管颈内动脉注射MPTP制作偏侧恒河猴帕金森病模型更为简单有效。

Objective To investigate a stable skill for preparing the hemiparkinsonism rhesus monkey model by unilateral internal carotid artery infusion of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Methods Ten healthy rhesus monkeys received MPTP injection through the internal carotid artery (ICA), 5 of them through common carotid artery (CCA) with the external carotid artery (ECA) clipped, the other 5 through direct arterial cannulation from CCA to ICA. One of the models received positron emission tomography (PET) examination pre-infusion and post-infusion respectively to observe the cerebral metabolism changes. The mesencephalon sections were studied immunohis- tochemically after perfusion. Results All the rhesus monkeys receiving CCA cannulation, as well as 2 rhesus monkeys through CCA injection with ECA clipped, developed the Parkinson's disease (PD) successfully. The other 3 rhesus monkeys through CCA injection with ECA clipped failed firstly, and developed PD eventually through subsequent direct CCA cannulation. PET showed the low metabolism in the basal ganglia region of the injected side. The tyrosine hydroxylase (TH)-immunoreactive neurons in the mesencephalon of the injection side were deformed and decreased, displaying significant difference with that in control side. Conclusion The monkey model of hemiparkinsonism could be induced by unilateral internal carotid artery infusion of MPTP. As MPTP could be infused into the internal carotid artery easily and completely, common carotid artery cannulation should be recommended in PD model induction of rhesus monkey.