H-Y1-2期帕金森病唇腺α-突触核蛋白病变与脑多巴胺转运体代谢对照的生物学标记物研究

发布时间：2018-02-09 16:28

本文关键词： 帕金森病唾液腺活检 α-突触核蛋白正电子发射型计算机断层显像　出处：《首都医科大学》2016年博士论文　论文类型：学位论文

【摘要】：【目的】旨在寻在帕金森病早期的外周病理生物学标记物,一方面检测H-Y1-2期帕金森病患者唇腺中是否存在特征性α-突触核蛋白(α-syn)聚集,另一方面通过多巴胺转运体-正电子发射型计算机断层显像(DAT-PET)进行影像代谢对照,以评估是否可以应用其作为PD的外周病理诊断标志物,从而提高PD的早期诊断水平及诊断的准确率。【方法】本研究连续筛选2013年9月-2015年2月在首都医科大学附属北京天坛医院运动障碍门诊就诊的帕金森病患者13例,年龄匹配的无锥体外系疾病者13例。PD患者进行H-Y分期和UPDRS评测。所有入组者均由同一口腔专科医师行唇腺活检取得组织,使用α-syn抗体/磷酸化α-syn抗体通过免疫组化染色方法检测唇腺组织中是否存在α-syn的异常聚集。此外,所有免疫反应阳性的切片均进行苏木精复染显示细胞核,以进一步明确唇腺组织中α-syn异常聚集的部位。同时所有入组者均进行DAT-PET检查,并分析其与患者唇腺活检病理结果的一致性,进行“周围”与“脑内”改变的对照。【结果】13名帕金森病患者中有9名的唇腺组织中α-突触核蛋白免疫反应阳性,而正常对照组则没有类似发现,α-syn异常沉积位于腺泡周边。所有入组PD患者及对照均未发现p-α-syn的异常沉积。12名PD患者的DAT-PET均可见在尾状核、前壳核和后壳核处11C-甲基-N-2β-甲基酯-3β-(4-氟-苯基)托烷(11C-CFT)不对称性摄取减低,包括9名免疫组化结果阳性的患者,正常对照组中仅有一例。以DAT-PET结果作为“金标准”,评估唇腺活检对PD诊断的的敏感性、特异性、阳性预测值、阴性预测值分别为75%、100%、100%和25%。【结论】我们的研究结果提供了更多地证据说明早期PD患者周围神经系统已经受累,唇腺组织中存在α-syn的异常沉积,且位于腺泡周边。唇腺中α-syn的异常聚集与脑内DAT-PET影像改变有很好的一致性。一方面唇腺中特征性α-syn聚集有望成为PD的外周病理诊断标志物,另一方面将唇腺活检与DAT-PET检查联合起来将会有助于提高PD的早期诊断率,这一结果仍需要大样本活检来进一步验证。
[Abstract]:[objective] to search for peripheral pathobiological markers in the early stage of Parkinson's disease (PD), on the one hand, to detect the presence of characteristic 伪 -synthase in the labial glands of patients with stage H-Y1-2 Parkinson's disease. On the other hand, the dopamine transporter-positron emission computed tomography (PET-PET) was used to evaluate whether it could be used as a peripheral pathological diagnostic marker for PD. [methods] from September 2013 to February 2015, 13 patients with Parkinson's disease were selected from Beijing Temple of Heaven Hospital affiliated to Capital Medical University. H-Y staging and UPDRS evaluation were performed in 13 patients with age matched extrapyramidal diseases. 伪 -syn antibody / phosphorylated 伪 -syn antibody was used to detect the abnormal aggregation of 伪 -syn in labial gland by immunohistochemical staining. In order to further determine the location of abnormal accumulation of 伪 -syn in labial gland tissue, all patients were examined by DAT-PET, and the results of pathological examination of labial gland biopsy were analyzed. [results] in 9 out of 13 Parkinson's disease patients, 伪 -synaptophysin immunoreactivity was positive in labial gland. The abnormal deposits of 伪 -syn were found in the acinar periphery in the normal control group. No abnormal deposits of p- 伪 -syn were found in the caudate nucleus in all the PD patients and the controls, and no abnormal deposits of p- 伪 -syn were found in the caudate nucleus. The asymmetric uptake of 11C- methyl-N-2 尾 -methyl ester -3 尾 -4-fluorophenyl) tropane 11C-CFT in anterior and posterior putamen decreased, including 9 patients with positive immunohistochemical results. The sensitivity, specificity, positive predictive value of labial gland biopsy for the diagnosis of PD were evaluated by using DAT-PET results as the "gold standard" in the normal control group. The negative predictive values were 75% and 25% respectively. [conclusion] our results provide more evidence that the peripheral nervous system has been involved in early PD patients and that abnormal deposits of 伪 -syn are present in the labial gland. The abnormal aggregation of 伪 -syn in labial gland is in good agreement with the changes of DAT-PET image in brain. On the one hand, the characteristic 伪 -syn aggregation in labial gland is expected to be a peripheral pathological diagnosis marker of PD. On the other hand, the combination of labial gland biopsy and DAT-PET examination will help to improve the early diagnosis rate of PD, and this result still needs to be further verified by a large sample biopsy.
【学位授予单位】：首都医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R742.5

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