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18F-ML-10PET/CT凋亡显像早期诊断帕金森病的实验研究

Early diagnosis of Parkinson's disease by PET/CT apoptosis imaging with tracer of 18F-ML-10

摘要目的 探讨18F-ML-10 PET/CT凋亡显像对帕金森病(PD)早期诊断的可行性. 方法 将20只健康成年雄性SD大鼠按随机数字表法分为对照组和实验组,每组10只.实验组经右侧纹状体注射6-羟基多巴胺(6-OHDA)制备大鼠PD早期模型.1周后通过阿扑吗啡诱导旋转实验进行大鼠行为学评估.采用11C-CFT、18F-ML-10 PET/CT显像分别观察大鼠纹状体多巴胺转运蛋白与黑质多巴胺能神经元凋亡情况,采用抗酪氨酸羟化酶(TH)抗体免疫荧光染色检测黑质致密部存活多巴胺能神经元数量,采用TUNEL凋亡染色检测黑质致密部凋亡多巴胺能神经元数量,采用Nissl染色观察神经细胞形态. 结果 1周后实验组大鼠明显向左侧旋转,平均旋转速度为(4.52±1.03)r/min.11C-CFT在实验组大鼠右侧纹状体与左侧纹状体的放射性摄取值比值为0.556±0.017,明显低于对照组(0.998±0.013),差异有统计学意义(P<0.05);18F-ML-10在实验组大鼠右侧黑质与左侧黑质的放射性摄取值比值为1.722±0.083,明显高于对照组(1.024±0.056),差异有统计学意义(P<0.05).免疫荧光染色显示实验组右侧黑质致密部与左侧黑质致密部的TH阳性神经元比值为0.528±0.012,明显低于对照组(1.036±0.030),差异有统计学意义(P<0.05).TUNEL凋亡染色显示实验组右侧黑质致密部凋亡多巴胺能神经元数量为43.200±2.507,明显高于对照组(1.400±0.427),差异有统计学意义(P<0.05). 结论 PD早期发病阶段与多巴胺能神经元凋亡有关.18F-ML-10 PET/CT凋亡显像部位与多巴胺能神经元凋亡部位具有一致性,有望用于PD早期的诊断.

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abstractsObjective The 18F-ML-10 PET/CT apoptosis imaging was taken in the early Parkinson's disease (PD) rat models.The feasibility of diagnosis of PD with 18F-ML-10 PET/CT apoptosis imaging is explored.Methods Twenty adult healthy male Sprague-Dawley rats were randomly divided into control group and PD model group (n=l 0).Intrastriat administration of 6-hydroxy dopamine (6-OHDA) was performed to induce progressive and retrograde degenerative changes in the substantial nigra of neurons (PD models).One week after apomorphine inducement,the rotational behaviors of the rats were evaluated.~C-CFT PET/CT imaging and 18F-ML-10 PET/CT were performed to observe the dopamine transport protein expression in the corpus striatum and apoptosis of dopaminergic neurons in the substantia nigra.Immunofluorescence staining of anti-tyrosine hydroxylase (TH) antibody was performed to evaluate the survival of dopaminergic cells in the compact part of substantia nigra.TUNEL was performed to evaluate the apoptosis of dopaminergic cells in the compact part of substantia nigra.Nissl staining was performed to detect the cellular morphology.Results One week after PD modeling,the rats in the experimental group obviously rotated to the contralateral,and the average rotation speed was (4.52 ±1.03) r/min.The ratio of 11C-CFT between the right and left striatum of rats in the experimental group was 0.556±0.017,which was significantly lower than that of the control group (0.998±0.013,P<0.05).The radioactivity ratio of'8F-ML-10 between the right and left substantia nigra of rats was 1.722±0.083,which was significantly higher than that of the control group (1.024±0.056,P<0.05).Immunofluorescence showed that the ratio of TH-positive neurons between the right and left compact part of substantia nigra in rats of the experimental group was 0.528 ±0.012,which was significantly lower than that of the control group (1.036±0.030,P<0.05).TUNEL showed that the number of dopaminergic neuronal apoptosis in the experimental group was 43.200±2.507,which was significantly larger than that of the control group (1.400±0.427,P<0.05).Conclusion PD is associated with apoptosis of dopaminergic neurons;18F-ML-10 PET/CT imaging can be used to diagnose PD in the early-stage.

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分类号 R742.5
栏目名称 基础研究
DOI 10.3760/cma.j.issn.1671-8925.2017.05.004
发布时间 2017-06-30
基金项目
天津市自然科学基金(13JCYBJC22000)武警后勤学院附属医院种子基金 Tianjin Natural Science Foundation of China Seed Fund of Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces
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中华神经医学杂志

中华神经医学杂志

2017年16卷5期

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