帕金森病猴模型纹状体多巴胺转运蛋白和多巴胺D_(2)受体显像的比较研究  

Comparative imaging study of striatal dopamine transporter and dopamine D_(2) receptor in MPTP-induced hemiparkinsonian monkeys

作　　者：陈生弟[1] 刘振国[1] 翁中芳[1] 孙文善[2] 沈鸣华[3] 方平 陈先文[1] 祖恒兵 李培勇[2] 

机构地区：[1]上海第二医科大学附属瑞金医院神经内科、帕金森病诊疗与研究中心 [2]上海第二医科大学附属瑞金医院核医学科 [3]上海医科大学药学院放射药理教研室 [4]无锡原子医学研究所

出　　处：《中华神经科杂志》2000年第4期10-13,65,共5页Chinese Journal of Neurology

基　　金：国家重点基础研究规划“脑功能和脑重大疾病的基础研究”资助项目(G1999054000);上海市卫生系统百名跨世纪优秀学科带头人培养计划资助项目(97BR001);上海市启明星计划资助项目(99QB14023);上海市科委青年科技“启明星后”计划资助项目(97QMB1410);上海市教委基金资助项目(99B08)。

摘　　要：目的　观察偏侧帕金森病 (PD)猴模型纹状体多巴胺转运蛋白 (DAT)和多巴胺D2 受体(D2 R)功能变化 ,探讨DAT和D2 R在PD诊断方面的临床意义。方法　利用DAT配体99mTc TRODAT 1【2 β N ,N 双 (2 硫乙基 )乙撑二胺基 ,3β (4氯苯基 )托烷】和D2 R配体1 31 I IBZM、1 31 I AIBZM【4 氨基 N (1 乙基 2 四氢吡咯基 )甲基 5 碘 2 甲氧基苯甲酰胺】、单光子发射体层摄影术 (SPECT)显像观察MPTP制备的偏侧PD猴模型纹状体的DAT和D2 R功能变化 ,并进行1 31 I IBZM【左旋 2 羟基 6 甲氧基 N (1 乙基 2 吡咯烷 )甲基苯酰胺】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)及其代谢产物浓度。HE染色光镜观察黑质纹状体的病理改变。结果　DATSPECT显像可见偏侧PD猴模型MPTP损毁侧纹状体的99mTc TRODAT 1放射性浓集缺失 ,D2 RSPECT显像则发现MPTP损毁侧与未损毁侧纹状体的1 31 I IBZM和1 31 I AIBZM放射性浓集无明显差别。放射自显影进一步证实了D2 RSPECT显像结果。生化和病理改变证实模型猴制备成功 ,且与DATSPECT显像结果相一致。结论　偏侧PD猴模型纹状体的DAT变化早于D2 R ,DATSPECT显像有助于对PD的早期诊断和病情监测。Objective To evaluate the clinical practice of dopamine transporter (DAT) and dopamine D 2 receptor (D 2R) for the diagnosis of Parkinson′s disease (PD)by measuring the activities of striatal DAT and D 2R of hemiparkinsonian monkeys. Methods DAT and D 2R imagings were performed by single photon emission computed tomography (SPECT) with 99m Tc TRODAT 1 and 131 I IBZM, 131 I AIBZM respectively in MPTP induced hemiparkinsonian monkey models with no apomorphine(APO) induced rotational behavior. 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 electrochemical detection (HPLC ECD). The histopathology was observed by microscopy and hematoxylin and eosin(HE) stain. Results The reduced uptake of 99m Tc TRODAT 1 in MPTP lesioned striatum was found by SPECT, as compared with that in intact one, but no difference of 131 I IBZM, 131 I AIBZM uptake was noted between the bilateral striata. The finding of autoradiography was in accordance with that of SPECT scanning with 131 I IBZM and 131 I IBZM. The neurochemical and neuropathological changes in hemiparkinsonian monkey model paralleled that of SPECT imaging with 99m Tc TRODAT 1. Conclusion The change of DAT is earlier than that of D 2R in the hemiparkinsonian monkey model with no APO induced rotational behavior. The SPECT imaging of striatal DAT is helpful for the early diagnosis of PD and for monitoring the progression of the disease.

关 键 词：帕金森病 载体蛋白质类 受体 多巴胺D_(2) 发射体层摄影术 发射型计算机 单光子 

分 类 号：R742.5[医药卫生—神经病学与精神病学]