Departments of Neurological Sciences, Rush Medical College, Chicago, Illinois 60612, USA.
Mov Disord. 2012 May;27(6):709-15. doi: 10.1002/mds.23838. Epub 2011 Jul 15.
The diagnosis of Parkinson's disease rests on motor signs of advanced central dopamine deficiency. There is an urgent need for disease biomarkers. Clinicopathological evidence suggests that α-synuclein aggregation, the pathological signature of Parkinson's disease, can be detected in gastrointestinal tract neurons in Parkinson's disease. We studied whether we could demonstrate α-synuclein pathology in specimens from unprepped flexible sigmoidoscopy of the distal sigmoid colon in early subjects with Parkinson's disease. We also looked for 3-nitrotyrosine, a marker of oxidative stress. Ten subjects with early Parkinson's disease not treated with dopaminergic agents (7 men; median age, 58.5 years; median disease duration, 1.5 years) underwent unprepped flexible sigmoidoscopy with biopsy of the distal sigmoid colon. Immunohistochemistry studies for α-synuclein and 3-nitrotyrosine were performed on biopsy specimens and control specimens from a tissue repository (23 healthy subjects and 23 subjects with inflammatory bowel disease). Nine of 10 Parkinson's disease samples were adequate for study. All showed staining for α-synuclein in nerve fibers in colonic submucosa. No control sample showed this pattern. A few showed light α-synuclein staining in round cells. 3-Nitrotyrosine staining was seen in 87% of Parkinson's disease cases but was not specific for Parkinson's disease. This study suggests a pattern of α-synuclein staining in Parkinson's disease that was distinct from healthy subjects and those with inflammatory bowel disease. The absence of this pattern in subjects with inflammatory bowel disease suggests it is not a sequel of inflammation or oxidative stress. 3-Nitrotyrosine immunostaining was common in all groups studied, suggesting oxidative stress in the colonic submucosa.
帕金森病的诊断依赖于中脑多巴胺缺乏的运动征象。目前迫切需要疾病生物标志物。临床病理证据表明，α-突触核蛋白聚集，即帕金森病的病理特征，可以在帕金森病的胃肠道神经元中检测到。我们研究了是否可以在未经准备的早期帕金森病患者的远端乙状结肠的柔性乙状结肠镜检查标本中证明α-突触核蛋白病理学。我们还寻找了 3-硝基酪氨酸，一种氧化应激的标志物。10 名未经多巴胺能药物治疗的早期帕金森病患者（7 名男性；中位年龄 58.5 岁；中位疾病持续时间 1.5 年）接受了未经准备的柔性乙状结肠镜检查，并对远端乙状结肠进行了活检。对活检标本和组织库对照标本（23 名健康受试者和 23 名炎症性肠病患者）进行了α-突触核蛋白和 3-硝基酪氨酸的免疫组织化学研究。10 名帕金森病患者中有 9 名样本适合研究。所有样本均显示结肠黏膜下层神经纤维中存在α-突触核蛋白染色。没有对照样本显示这种模式。少数样本中圆形细胞显示轻度α-突触核蛋白染色。87%的帕金森病病例显示 3-硝基酪氨酸染色，但这种模式不是帕金森病特有的。这项研究表明帕金森病中存在一种不同于健康受试者和炎症性肠病患者的α-突触核蛋白染色模式。在炎症性肠病患者中没有这种模式，提示它不是炎症或氧化应激的后果。所有研究组中 3-硝基酪氨酸免疫染色都很常见，提示结肠黏膜下层存在氧化应激。
