更多内容请点击

中国全科医学

• •

Wilson病患者血清RAGE/NF-κB通路表达水平变化及其对轻度认知损害的影响

倪明珠, 王莉, 许珍晶, 石桥, 侯志峰*   

  1. 23031 安徽省合肥市，安徽中医药大学第一附属医院脑病中心
  • 收稿日期:2025-03-18 接受日期:2025-04-08
  • 通讯作者: 侯志峰
  • 基金资助:
    基于“脾-线粒体-炎症微环境”探讨mtDNA介导的Wilson病TX小鼠认知损害神经元损伤机制及健脾化痰祛瘀方的干预研究(82405176); 黄蒲通窍胶囊调控mtDNA介导炎症衰老治疗衰老相关认知下降作用机制研究(2024YFYLCZX18); 2023年引进高层次人才倪明珠(ahgccrcjb20240297)

Changes in Serum RAGE/NF-κB Pathway Expression Levels in Wilson’s Disease Patients and Their Impact on Mild Cognitive Impairment

Ni Mingzhu, Wang Li, Xu Zhenjing, Shi Qiao, Hou Zhifeng*   

  • Received:2025-03-18 Accepted:2025-04-08
分享到

摘要： 背景 Wilson病（WD）炎症水平增高且与认知损害密切相关。研究表明，晚期糖基化终产物受体（RAGE）/核因子κB（NF-κB）信号通路的激活是介导认知障碍的重要炎症机制，但其在WD伴轻度认知障碍（MCI）患者血清的表达水平尚不清楚。目的 探讨Wilson病患者血清RAGE/NF-κB通路表达水平变化及其对轻度认知损害的影响。方法 收集2024年1月至2025年1月在安徽中医药大学第一附属医院脑病中心住院的23例WD伴MCI患者为WD-MCI组。选取同期年龄、性别、受教育程度相匹配的认知功能正常的健康体检者23例为对照组。采用简易精神状态检查量表（MMSE）、霍普金斯语言学习测试（HVLT）、波士顿命名测试第二版（BNT-2）、画钟测试（CDT）、连线测试-A（TMT-A）、工具性日常生活能力量表（IADL）分别对患者的整体认知状态和记忆、语言、视空间、执行、日常生活能力进行评价。应用酶联免疫吸附法和qRT-PCR测定血清RAGE/NF-κB信号通路关键分子表达水平。比较两组认知功能、血清RAGE水平及NF-κBp65 mRNA表达水平的差异。采用Pearson检验分析血清RAGE水平、NF-κBp65 mRNA表达水平与认知功能评分的相关性。结果 与对照组相比，WD-MCI组MMSE、HVLT、BNT-2、CDT评分均明显降低，TMT-A、 IADL评分均显著升高（P<0.05）。WD-MCI组血清RAGE水平、NF-κBp65 mRNA表达水平均高于对照组（P<0.05）。Pearson相关分析显示，血清NF-κBp65 mRNA表达水平血清RAGE水平及NF-κBp65 mRNA表达水平与MMSE（r=-0.866，-0.729）、HVLT（r=-0.721，-0.728）、BNT-2（r=-0.381，-0.382）、CDT（r=-0.788，-0.709）评分呈负相关，与TMT-A（r=0.774，0.524）、IADL（r=0.433，0.376）评分呈正相关（P<0.05）。结论 Wilson病患者血清RAGE/NF-κB通路表达水平明显增高，且与认知功能损害呈显著正相关。

关键词: Wilson病, 轻度认知障碍, 炎症, 晚期糖基化终产物受体, 核因子κB

Abstract: Background Wilson's disease (WD) is associated with elevated inflammatory levels and closely linked to cognitive impairment. Studies suggest that activation of the receptor for advanced glycation end products (RAGE)/nuclear factor kappa B (NF-κB) signaling pathway is a critical inflammatory mechanism mediating cognitive dysfunction, yet its expression in serum of WD patients with mild cognitive impairment (MCI) remains unclear. Objective To investigate changes in serum RAGE/NF-κB pathway expression and their impact on MCI in WD patients. Methods A total of 23 WD patients with MCI (WD-MCI group) hospitalized at the Encephalopathy Center of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2024 to January 2025 were enrolled. Age-, sex-, and education-matched healthy controls (n=23) were recruited. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test (HVLT), Boston Naming Test-Second Edition (BNT-2), Clock Drawing Test (CDT), Trail Making Test-A (TMT-A), and Instrumental Activities of Daily Living Scale (IADL). Serum RAGE levels and NF-κB p65 mRNA expression were measured using enzyme-linked immunosorbent assay (ELISA) and qRT-PCR, respectively. Differences in cognitive scores, serum RAGE levels, and NF-κB p65 mRNA expression between groups were compared. Pearson correlation analysis evaluated associations between RAGE/NF-κB p65 mRNA levels and cognitive scores. Results Compared with controls, the WD-MCI group showed significantly lower MMSE, HVLT, BNT-2, and CDT scores, and higher TMT-A and IADL scores (P<0.05). Serum RAGE levels and NF-κB p65 mRNA expression were elevated in the WD-MCI group (P<0.05). Pearson analysis revealed that serum RAGE levels and NF-κB p65 mRNA expression negatively correlated with MMSE (r=-0.866，-0.729), HVLT (r=-0.721，-0.728), BNT-2 (r=-0.381，-0.382), and CDT(r=-0.788，-0.709)scores, and positively correlated with TMT-A (r=0.774，0.524)and IADL (r=0.433，0.376) scores (P<0.05). Conclusion WD patients exhibit increased serum RAGE/NF-κB pathway activity, which is significantly associated with mild cognitive impairment.

Key words: Wilson's disease, mild cognitive impairment, inflammation, receptor for advanced glycation end products, nuclear factor kappa-B

冀ICP备12018774号-6　冀公网安备 13040302001295号　网站版权 © 《中国全科医学》编辑部　技术支持：北京玛格泰克科技发展有限公司