帕金森病患者血浆神经病理性蛋白及炎症因子与便秘的相关性

Correlation of plasma neuropathological proteins and inflammatory factors with constipation in Parkinson’s disease patients

摘要

目的：探讨帕金森病（Parkinson’s disease，PD）患者血浆神经病理性蛋白及炎症因子与便秘的相关性。方法：连续收集就诊于淮安市第一人民医院神经内科的88例PD患者，通过统一帕金森病评定量表（unified Parkinson disease rating scale，UPDRS）、汉密尔顿焦虑量表（Hamilton anxiety scale，HAMA）、汉密尔顿抑郁量表（Hamilton depression scale，HAMD）等评估运动和非运动症状，根据Wexner便秘评分将PD患者分为PD伴便秘（PD with constipation，PD-C）组和PD不伴便秘（PD without constipation，PD-NC）组。同期选择年龄、性别匹配的健康对照者30例作为健康对照（healthy control，HC）组。利用ELISA技术检测受试者血浆α-突触核蛋白（α-synuclein，α-syn）、磷酸化-α-syn（phosphorylated α-syn，p-α-syn）、胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）、S100钙结合蛋白B（S100 calcium binding protein B，S100B）、神经丝轻链（neurofilament light chain，NfL）、肿瘤坏死因子（tumor necrosis factor，TNF）-α及白细胞介素（interleukin，IL）-18、IL-1β水平。使用SPSS 29.0及R软件进行统计分析，采用t检验及Mann-Whitney U检验比较两组间临床资料和各生物学指标的差异，使用Logistic回归分析PD伴便秘发生的危险因素，基于GFAP的不同生物标志物组合预测PD便秘发生的受试者工作特征曲线。结果：PD-C组血浆GFAP、S100B、TNF-α、IL-18、IL-1β水平均高于PD-NC组，差异有统计学意义（P均< 0.05）。在校正年龄与生活方式后，多因素分析结果显示GFAP、S100B和IL-1β是PD患者发生便秘的独立危险因素。基于此构建的联合预测模型具有良好的诊断效能。结论：PD患者便秘的发生可能与外周神经胶质细胞激活介导的炎症反应相关。

Abstract

Objective：To explore the correlation between plasma neuropathological proteins and inflammatory factors with constipation in patients with Parkinson’s disease（PD）. Methods：A total of 88 patients with PD were recruited from the Department of Neurology at the Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University. Motor and non-motor symptoms were assessed using the unified Parkinson’s disease rating scale（UPDRS），the Hamilton anxiety scale（HAMA），the Hamilton depression scale（HAMD），and other validated scales. According to the Wexner constipation score，PD patients were divided into PD patients with constipation（PD-C）and PD patients without constipation（PD-NC）. During the same period，30 healthy individuals matched in age and sex were enrolled as the control group（HC）. Plasma levels of α-synuclein（α-syn），phosphorylated α-syn（p-α-syn），neurofilament light chain（NfL），glial fibrillary acidic protein（GFAP），S100 calcium-binding protein B（S100B），tumor necrosis factor（TNF）-α，interleukin（IL）-18，and IL-1β were measured by ELISA. Statistical analyses were performed using SPSS 29.0 and R software. Group differences were compared usingt-tests and Mann-Whitney U tests. Binary Logistic regression was used to identify risk factors for constipation，and receiver operating characteristic curves were constructed to evaluate the predictive performance of biomarker combinations based on GFAP. Results：Plasma levels of GFAP，S100B，TNF-α，IL-18，and IL-1β were significantly higher in the PD-C group（all P<0.05）. After adjusting for age and lifestyle，multivariate analysis identified GFAP，S100B，and IL-1β as independent risk factors for constipation in PD. The combined predictive model based on these factors exhibited favorable diagnostic performance. Conclusion：Constipation in PD patients may be related to inflammatory reaction mediated by activation of peripheral neuroglial cells.

关键词

帕金森病 / 便秘 / 胶质纤维酸性蛋白 / S100钙结合蛋白B / 白细胞介素-1β / 神经胶质细胞

Key words

Parkinson’s disease / constipation / glial fibrillary acidic protein / S100 calcium-binding protein B / interleukin-1β / neuroglial cell

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基金资助

江苏省卫生健康委员会面上项目(M2022082)

淮安市神经退行性疾病重点实验室项目(HAP202401)