帕金森病猴模型纹状体多巴胺D_(2)受体的显像研究

The experimental study on the activity of striatal dopamine D_(2) receptor in parkinsonism monkey model

目的 应用碘标左旋 2 羟基 6 甲氧基 N 〔(1 乙基 2 吡咯烷 )甲基〕苯酰胺 (131I IBZM)及 4 氨基 N (1 乙基 2 甲氢吡咯基 )甲基 5 碘 2 甲氧基苯甲酰胺 (12 3I AIBZM)单光子发射体层摄影术(SPECT)观察一侧帕金森病 (PD)猴模型纹状体多巴胺D2 受体 (D2 R)功能变化 ,探讨12 3I AIBZMSPECTD2 R功能显像的临床意义及其可行性。 方法 恒河猴M1、M2 、M3,其中M1、M2 为经右侧颈总动脉注射 1 甲基 4 苯基 1,2 ,3,6 四氢吡啶 (MPTP)建立的一侧PD模型猴 ,M3 为正常猴 ,静脉注射131I IBZM或12 3I AIBZM后进行SPECT显像 ,并进行131I IBZM放射自显影观察。高效液相色谱 电化学法检测离体尾、壳核及黑质多巴胺 (DA)及其代谢产物含量 ,HE染色光镜观察其病理改变。 结果 SPECT显像可见纹状体、伏隔核及嗅结节有放射性浓集 ,阿朴吗啡 (APO)未诱发出旋转行为的模型猴纹状体及各脑叶放射性浓集左、右侧未见明显差别 ,放射自显影进一步证实这一结果。MPTP损毁侧尾、壳核及黑质DA含量较健侧分别降低 98 9%、99 1%和 81 4% ,光镜下可见MPTP损毁侧的黑质细胞数量减少 ,残存细胞变性。 结论 12 3I AIBZMSPECT显像能反映D2 R功能状态 ,可能是预测PD患者对左旋多巴 ,尤其是D2

Objective The functional change of striatal dopamine D 2 receptor (D 2R) in hemiparkinsonian monkey model was investigated by single photon emission computed tomography(SPECT) imaging with 131 I IBZM and 123 I AIBZM, and the clinical value and feasibility of D 2R SPECT imaging with 123 I AIBZM were evaluated. Methods Three rhesus monkeys, named M 1,M 2,M 3, were used for this experiment. M 1 and M 2 were hemiparkinsonian monkey models induced by the unilateral infusion of MPTP into the right common carotid artery. M 3 was normal monkey. SPECT imaging was performed after an injection of 131 I IBZM or 123 I AIBZM. The brain tissue sections were imaged by autoradiography with 131 I IBZM. The levels of dopamine (DA) and its metabolites were measured by high performance liquid chromatography and electro chemical detection (HPLC ECD). The neuropathological change was observed with hematoxylin and eosin (HE) staining under microscopy. Results The SPECT scan demonstrated that the radiotracers were concentrated in the striatum, accumber nucleus, and olfactory tube. No difference of the radiotracer uptake in the striatum and cortexs was found between MPTP lesioned side and the intact side in the hemiparkinsonian monkeys, and no rotational behavior induced by apomorphine (APO) was observed. These results were in good accordance with the findings by 131 I IBZM autoradiography. The levels of DA in the putamen, caudate nucleus and substantia nigra of MPTP lesioned side were reduced by 98 9%, 99 1% and 81 4% respectively, as compared with those of the intact side. The cell number was reduced and the degeneration of the remained cells in the substantia nigra and striatum of MPTP lesioned side were observed by microscopy. Conclusions The SPECT imaging with 123 I AIBZM reflected the functional actitvity of striatal D 2R and might be valuable for predicting the patients’ response to L dopa, especially D 2R agonist therapy for Parkinson’s disease.