原发性帕金森病患者血清标志物及疼痛程度与认知功能的相关性

doi:10.3760/cma.j.cn441417-20240000-04016

摘要/Abstract

摘要：

目的　探讨原发性帕金森病患者血清中白细胞介素-1β（IL-1β）、α-突触核蛋白和硫氧还蛋白硫过氧化物酶（TPX）的表达水平及疼痛与认知功能损害的相关性。方法　本研究采用回顾性分析，收集2021年3月至2024年3月期间西安市红会医院收治的124例原发性帕金森病患者的临床资料。其中男75例、女49例，年龄（63.84±7.47）岁。根据认知功能状态分为PDCI组（51例，痴呆）和PDNC组（73例，轻微认知障碍和无认知障碍）。通过酶联免疫吸附试验法测定两组间血清IL-1β、α-突触核蛋白和TPX的表达水平，采用蒙特利尔认知评估量表（MoCA）、KINGS帕金森病疼痛量表（KPPS）对患者认知功能与疼痛症状进行评分，采用Pearson相关性分析认知功能与血清IL-1β、α-突触核蛋白、TPX表达水平及KPPS评分的相关性。通过受试者操作特征曲线（ROC）评估IL-1β、α-突触核蛋白、TPX水平及KPPS评分在评估原发性帕金森患者发生痴呆中的价值。采用配对t检验、χ²检验进行统计分析。结果　PDCI组患者年龄大于PDNC组，血清IL-1β和α-突触核蛋白水平及KPPS评分高于PDNC组，TPX水平低于PDNC组（均P<0.05）。PDCI组患者的MoCA量表各维度及总分均低于PDNC组（均P<0.05）。MoCA总分与血清IL-1β、α-突触核蛋白和KPPS评分存在负相关（r=-0.413、-0.553、-0.691，均P<0.05），MoCA总分与血清TPX存在正相关（r=0.799，P<0.05）。ROC表明，IL-1β、α-突触核蛋白、TPX及KPPS评分联合预测的曲线下面积（AUC）值为0.973，灵敏度为98.0%，特异度为97.3%。结论　血清IL-1β、α-突触核蛋白和TPX的表达异常及疼痛症状与原发性帕金森病患者的认知功能损害密切相关。

关键词:

白细胞介素-1β, α-突触核蛋白, 硫氧还蛋白硫过氧化物酶, 认知功能, 疼痛, 原发性帕金森病

Abstract:

Objective　To investigate the correlation of cognitive function with the levels of interleukin-1β (IL-1β), α-synuclein, and thioredoxin peroxidase (TPX) and pain in patients with primary Parkinson's disease. Methods　This was a retrospective study. The clinical data of 124 patients with primary Parkinson's disease treated at Xi'an Honghui Hospital between March 2021 and March 2024 were collected. Among them, there were 75 males and 49 females, with an age of 63.84±7.47. According to their cognitive function, they were divided into a PDCI group (51 cases, dementia) and a PDNC group (73 cases, mild cognitive impairment and no cognitive impairment). The serum levels of IL-1β, α-synuclein, and TPX in both groups were measured using the enzyme linked immunosorbent assay. The Montreal Cognitive Assessment (MoCA) and KINGs' Parkinsons' Disease Pain Scale (KPPS) were used to evaluate their cognitive function and pain. The receiver operating characteristic curve (ROC) was used to assess the value of the levels of IL-1β, α-synuclein, and TPX and score of KPPS in the evaluation of incidence of dementia. Paired t and χ² tests were used for the statistical analysis. Results　The patients in the PDCI group were older than the patients in the PDNC group (P<0.05). The serum levels of IL-1β and α-synuclein and score of KPPS in the PDCI group were higher were higher than those in the PDNC group (all P<0.05). The level of TPX in the PDCI group was lower than that in the PDNC group (P<0.05). The scores of all the dimensions and total score of MoCA in the PDCI group were lower than those in the PDNC group (all P<0.05). The total score of MoCA was negatively correlated with serum IL-1β and α-synuclein and score of KPPS (r=-0.413, -0.553, and -0.691; all P<0.05), and positively with serum TPX (r=0.799; P<0.05). The ROC analysis indicated that the combination of IL-1β, α-synuclein, TPX, and score of KPPS had an area under the curve of 0.973, a sensitivity of 98.0%, and a specificity of 97.3%. Conclusion　The abnormal expression of serum IL-1β, α-synuclein, and TPX, as well as pain symptoms, are closely related to cognitive impairment in patients with primary Parkinson's disease.

Key words:

Interleukin-1β, α-synuclein, Thioredoxin peroxidase, Cognitive function, Pain, Primary Parkinson's disease

王煜胡晓辉马洁崔鑫李婷.

原发性帕金森病患者血清标志物及疼痛程度与认知功能的相关性 [J]. 国际医药卫生导报, 2025, 31(4): 603-607.

Wang Yu, Hu Xiaohui, Ma Jie, Cui Xin, Li Ting.

Correlation of cognitive function with serum biomarkers and pain degree in patients with primary Parkinson's disease [J]. International Medicine and Health Guidance News, 2025, 31(4): 603-607.

参考文献

[1] 蔡金凤,王洪财,葛汝丽. 肠道菌群失衡在帕金森病α-突触核蛋白诱导小胶质细胞活化中的作用[J]. 国际医药卫生导报,2023,29(22):3153-3157. DOI:10.3760/cma.j.issn.1007-1245.2023.22.001.
[2] Rosenblum S, Meyer S, Richardson A, et al. Capturing subjective mild cognitive decline in Parkinson's disease[J]. Brain Sci, 2022,12(6):741. DOI: 10.3390/brainsci12060741.
[3] 陈苗,张岗,王文佳,等. 合成MRI联合VBM脑分区在早期帕金森病诊断中的应用[J]. 磁共振成像,2023,14(10):20-25. DOI:10.12015/issn.1674-8034.2023.10.004.
[4] 黄荣,李晓晖,陈文武. 重复经颅磁刺激联合帕罗西汀对帕金森合并抑郁患者认知、情绪及血清5-HT、IL-1β水平的影响[J]. 国际精神病学杂志,2023,50(3):466-468,472.
[5] Espay AJ, Lees AJ. Loss of monomeric alpha-synuclein (synucleinopenia) and the origin of Parkinson's disease[J]. Parkinsonism Relat Disord, 2024,122:106077. DOI: 10.1016/j.parkreldis.2024.106077.
[6] 贺晓琴,黄文琴,王燕萍. 帕金森病患者血清胱抑素C、转铁蛋白及抗氧化酶水平与认知功能损伤的相关性[J]. 广州医科大学学报,2022,50(4):71-74. DOI:10.3969/j.issn.2095-9664.2022.04.14.
[7] Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease[J]. Mov Disord, 2015,30(12):1591-1601. DOI: 10.1002/mds.26424.
[8] Chaudhuri KR, Rizos A, Trenkwalder C, et al. King's Parkinson's disease pain scale, the first scale for pain in PD: an international validation[J]. Mov Disord, 2015,30(12):1623-1631. DOI: 10.1002/mds.26270.
[9] 王盼,张熙,周波,等. 蒙特利尔认知评估量表的验证性因素分析[J]. 中华保健医学杂志,2012,14(2):101-103. DOI:10.3969/j.issn.1674-3245.2012.02.006.
[10] Furgiuele A, Pereira FC, Martini S, et al. Dopaminergic regulation of inflammation and immunity in Parkinson's disease: friend or foe? [J]. Clin Transl Immunology, 2023,12(10):e1469. DOI: 10.1002/cti2.1469.
[11] 常燕,张熙琬,王媛,等. 早发型与晚发型帕金森病多巴胺能神经元和脑葡萄糖代谢变化差异[J]. 中国医学影像技术,2023,39(10):1445-1449. DOI:10.13929/j.issn.1003- 3289. 2023.10.002.
[12] Algotsson C, Rosso A, Elmståhl S, et al. Prevalence and functional impact of parkinsonian signs in older adults from the Good Aging in Skåne study[J]. Parkinsonism Relat Disord, 2023,111:105416. DOI: 10.1016/j.parkreldis.2023.105416.
[13] 王海州,杨紫葵,陈璐,等. 震颤分析应用于帕金森病鉴别诊断中的准确性及价值[J]. 临床与病理杂志,2023,43(3):490-495. DOI:10.11817/j.issn.2095-6959.2023.222392.
[14] 许叶,王埮,陈志斌. 帕金森病常见睡眠障碍的研究进展[J]. 中国老年学杂志,2023,43(1):221-226. DOI:10.3969/j.issn.1005-9202.2023.01.053.
[15] 刘美辰,解敬慧,浦兰兰,等. 正电子发射断层扫描成像对帕金森病症状评估的研究进展[J]. 中华神经医学杂志,2016,15(3):315-318. DOI:10.3760/cma.j.issn.1671-8925. 2016.03.022.
[16] Jung NY, Park KH, Seo SW, et al. Survival in Korean patients with frontotemporal dementia syndrome: association with behavioral features and Parkinsonism[J]. J Clin Med, 2022,11(8):2260. DOI: 10.3390/jcm11082260.
[17] Gandhi P, Plowman EK, Steele CM. Comparison of lingual pressure generation capacity in Parkinson disease, amyotrophic lateral sclerosis, and healthy aging[J]. Am J Speech Lang Pathol, 2022,31(4):1845-1853. DOI: 10.1044/2022_AJSLP-21-00385.
[18] Cheng G, Liu Y, Ma R, et al. Anti-Parkinsonian therapy: strategies for crossing the blood-brain barrier and nano-biological effects of nanomaterials[J]. Nanomicro Lett, 2022,14(1):105. DOI: 10.1007/s40820-022-00847-z.
[19] 郝梦蝶,郑伊桐,张利杰,等. 血脑屏障与帕金森病的研究进展[J]. 卒中与神经疾病,2023,30(3):325-328. DOI:10.3969/j.issn.1007-0478.2023.03.021.
[20] 赵丽丽,高健,张硕,等. 前驱性便秘的帕金森病患者血清炎性因子IL-6、IL-1β及IL-17的变化及其临床意义[J]. 中国老年学杂志,2024,44(4):845-847. DOI:10.3969/j.issn. 1005-9202.2024.04.023.
[21] Yang J, Du C, Li Y, et al. Contrasting iron metabolism in undifferentiated versus differentiated MO3.13 oligodendrocytes via IL-1β-induced iron regulatory protein 1[J]. Neurochem Res, 2024,49(2):466-476. DOI: 10.1007/s11064-023-04047-y.
[22] Pan L, Li C, Meng L, et al. Tau accelerates α-synuclein aggregation and spreading in Parkinson's disease[J]. Brain, 2022,145(10):3454-3471. DOI: 10.1093/brain/awac171.
[23] Abdallah EAA, Almilaibary A, El-Refaei MF. Fagonia indica ameliorates chromium-induced nephrotoxicity: Role of antioxidant activity and pro-inflammatory cytokines in in-vivo renoprotection[J]. Arch Environ Occup Health, 2023,78(5):289-303. DOI: 10.1080/19338244.2023.　2185189.
[24] Huang LC, Chen LG, Wu PA, et al. Effect of deep brain stimulation on brain network and white matter integrity in Parkinson's disease[J]. CNS Neurosci Ther, 2022,28(1):92-104. DOI: 10.1111/cns.13741.
[25] 杨小鸥,杨国伟,刘志孝,等. 白藜芦醇通过PI3K/Akt/GSK-3β通路对6-OHDA致帕金森病小鼠神经退行性病变改善的作用研究[J]. 中西医结合心脑血管病杂志,2020,18(12):1880-1883. DOI:10.12102/j.issn.1672-1349. 2020.12.009.
[26] Dick F, Tysnes OB, Alves GW, et al. Altered transcriptome-proteome coupling indicates aberrant proteostasis in Parkinson's disease[J]. iScience, 2023,26(2):105925. DOI: 10.1016/j.isci.2023.105925.
[27] 章雨桐,王秋琴,徐语晨,等. 帕金森病患者疼痛影响因素的系统评价[J]. 中国全科医学,2023,26(14):1766-1774. DOI:10.12114/j.issn.1007-9572.2022.0788.
[28] Vila-Chã N, Cavaco S, Mendes A, et al. Central pain in Parkinson's disease: behavioral and cognitive characteristics[J]. Parkinsons Dis, 2021,2021:5553460. DOI: 10.1155/2021/5553460.
[29] Singh A, Kandi AR, Jayaprakashappa D, et al. The transcriptional response to oxidative stress is independent of stress-granule formation[J]. Mol Biol Cell, 2022,33(3):ar25. DOI: 10.1091/mbc.E21-08-0418.