Singaram C, Ashraf W, Gaumnitz E A, Torbey C, Sengupta A, Pfeiffer R, Quigley E M
Department of Internal Medicine, University of Wisconsin, Madison 52705, USA.
Lancet. 1995 Sep 30;346(8979):861-4. doi: 10.1016/s0140-6736(95)92707-7.
Clinical studies suggest that gut disorders are common in Parkinson's disease, but the morphological basis is unknown. Depletion of dopamine-containing neurons in the central nervous system is a basic defect in Parkinson's disease. We compared colonic tissue from 11 patients with advanced Parkinson's disease, 17 with adenocarcinoma (normal tissue was studied), and five who underwent colectomy for severe constipation. Immunohistochemistry was used to stain myenteric and submucosal neurons for dopamine, tyrosine hydroxylase, and vasoactive intestinal polypeptide (VIP). Each class of neurons was quantified as a percentage of the total neuronal population stained for the marker protein gene product 9.5. Nine of the 11 Parkinson's disease patients had substantially fewer dopaminergic myenteric neurons than the other subjects (mean 0.4 [SE 0.2] vs 6.9 [2.3] in controls and 5.7 [2.0] in constipated subjects). There was very little difference between the groups in numbers of tyrosine-hydroxylase and VIP neurons. Two Parkinson's disease patients had similar distributions of all types of neurons, including dopaminergic myenteric neurons, to the controls. High-performance liquid chromatography showed lower levels of dopamine in the muscularis externa (but not mucosa) in four Parkinson's disease patients than in four controls (7.3 [5.1] vs 24.2 [4.6] nmol per g protein), but levels of dopamine metabolites were similar in the two groups. The identification of this defect of dopaminergic neurons in the enteric nervous system in Parkinson's disease may lead to better treatment of colorectal dysfunction in this disease.
临床研究表明，肠道疾病在帕金森病中很常见，但形态学基础尚不清楚。中枢神经系统中含多巴胺神经元的耗竭是帕金森病的一个基本缺陷。我们比较了11例晚期帕金森病患者、17例腺癌患者（研究正常组织）和5例因严重便秘接受结肠切除术患者的结肠组织。采用免疫组织化学法对肌间神经丛和黏膜下神经元进行多巴胺、酪氨酸羟化酶和血管活性肠肽（VIP）染色。每类神经元被量化为标记蛋白基因产物9.5染色的总神经元群体的百分比。11例帕金森病患者中有9例的多巴胺能肌间神经丛神经元明显少于其他受试者（帕金森病患者组均值为0.4[标准误0.2]，对照组为6.9[2.3]，便秘患者组为5.7[2.0]）。酪氨酸羟化酶神经元和VIP神经元数量在各组之间差异很小。2例帕金森病患者所有类型神经元（包括多巴胺能肌间神经丛神经元）的分布与对照组相似。高效液相色谱法显示，4例帕金森病患者的肌层（而非黏膜）中多巴胺水平低于4例对照组（分别为7.3[5.1]和24.2[4.6]nmol/g蛋白），但两组多巴胺代谢产物水平相似。帕金森病患者肠道神经系统中多巴胺能神经元这一缺陷的发现可能会带来对该疾病结直肠功能障碍更好的治疗方法。
