帕金森病患者脑标本黑质、纹状体内多巴胺转运体蛋白的表达

Altered expression of dopamine transporter in substantia nigra and striatum in postmortem human brain of Parkinson’s disease

目的观察帕金森病(PD)患者脑标本黑质、纹状体多巴胺转运体(DAT)的表达。方法以免疫放射自显影显示DAT在黑质、纹状体的分布。结果正常人脑标本DAT强标记信号分布于黑质、壳核和尾状核。在PD患者脑标本,正常分布于壳核的DAT几乎均消失;尾状核DAT降低以背外侧部为主;黑质DAT标记减少程度轻于壳核、尾状核,以黑质腹侧区和外侧区为主。定量分析发现DAT强度在壳核比对照组降低90.9%(P<0.01),在尾状核背外侧降低66.7%(P<0.01);所分析黑质5个亚区的腹侧区和外侧区DAT表达降低明显,标记强度比对照组分别下降50.0%和35.9%(P<0.05,P<0.01);另3个亚区有降低趋势,差异无统计学意义。结论DAT在PD患者脑标本壳核及尾状核表达显著降低,为临床应用DAT配基显像技术诊断PD提供了直接的形态学依据。

Objective To study the altered expression of dopamine transporter （DAT） in substantia nigra and striatum in postmortem human brain of Parkinson＇ s disease （PD） . Methods Immunoautoradiography was used to reveal DAT distribution in postmortem human brain. Results Strongly labeling signal of DAT was mainly found in the substantia nigra, the putamen and the candate nucleus in controls. In contrast, it was drastically reduced in the putmen and the dorsolateral caudate nuclus in PD brains, but the ventromedial part of the caudate nucleus showed a significant sparing adjacent to the border of the lateral ventricle. In the substantia nigra, the ventral and the lateral parts of the substantia nigra showed an obvious decreasing of DAT and the reducing degree of DAT labeling signals in those regions is smaller than that in the putamen and the candate nucleus. Quantitative analysis revealed that 90.9% and 66. 7% of the labeling intensity of DAT were decreased in the putamen and the caudate nucleus as comparing with the corresponding controls respectively （ P 〈 0. 01 ）. Among the five regions studied of the substantia nigra, DAT labeling decreased 50. 0% and 35.9% of the corresponding controls respectively in the ventral （ P 〈 0. 05 ） and the lateral regions of substantia nigra （ P 〈 0. 01 ） , while the dorsal region of substantia nigra, parabrachial pigmented nucleus and the medial region of substantia nigra only showed a decreasing trend of DAT labeling without significant difference as comparing with the controls respectively. Conclusions DAT expression should be drastically reduced in putamen and caudate nucleus in postmortem PD human brain, which provide the morphological evidence for PET/SPECT imaging by using DAT ligands in diagnosis of PD.