通讯作者: 张丽霞, 853362460@qq.com

DOI：10.12201/bmr.202412.00077

Correlation between SIRT1/NF-κB signaling pathway and cognitive impairment in patients with Parkinsons disease

• 摘要：【摘要】目的：研究帕金森病(Parkinson disease，PD)患者沉默信息调节因子2相关酶1/核因子κB(Silent mating type information regulation 2 homolog 1/Nuclear factor κB,SIRT1/NF-κB)信号通路与认知功能损害(Cognitive impairment, CI)的相关性及诊断意义。方法：选取台州市第二人民医院2017年9月到2021年3月住院的119例PD患者，记为PD组，根据研究对象认知功能障碍及诊断指南将所纳入研究对象分为PD认知功能正常(Normal cognitive, NC)33例、PD轻度认知功能障碍(Mild cognitive impairment ,MCI)58例、帕金森病痴呆( Dementia in Parkinson disease, PDD )28例。此外，同期来院体检的50例健康者为正常对照组。入院后检测所有受试者外周血中SIRT1/NF-κB信号通路相关分子表达水平，并通过偏相关分析法分析PD患者SIRT1/NF-κB信号通路表达与认知功能的关系，对CI的影响因素分析采用Cox比例风险回归模型分析，同时采用受试者工作特征(Receiver operating characteristic, ROC)曲线以评价SIRT1/NF-κB信号通路相关分子表达对PD患者继发CI的诊断效能。结果：PD患者不同亚组受教育程度、病程、H-Y（Hoehn-Yahr）分期、UPDRS-Ⅲ（Unified Parkinson’s Disease Rating Scale-Ⅲ）、MoCA(Montreal Cognitive Assessment)总分等基线资料差异有统计学意义(P<0.05)；PD组患者SIRT1 mRNA(messenger RNA)表达均显著低于正常组，NF-κB mRNA表达则高于对照组(P<0.05)，进一步对PD组患者进行分层比较，发现PDD组患者SIRT1mRNA表达均显著低于PD-MCI组、PD-NC组，PD-MCI组患者上述指标表达亦显著低于PD-NC组(P<0.05)，采用偏相关分析法，发现SIRT1、NF-κB mRNA与MoCA评分之间仍存在明显相关性(r=0.637、-0.527，P<0.05)；Cox回归分析结果显示，高H-Y分期以及高表达NF-κB mRNA为影响PD患者发生CI的独立危险因素，高表达SIRT1 mRNA、高教育程度为PD患者发生CI的独立保护因素；ROC曲线显示，SIRT1、NF-κB mRNA表达均可以诊断PD患者继发CI(P＜0.05)，两者具有良好的预测作用，此时其AUC、敏感度、特异度分别为0.875、86.81%、90.36%。结论：SIRT1、NF-κBmRNA在PD继发CI患者外周血中高表达， 认知功能有较强的相关性，早期加强PD患者外周血SIRT1、NF-κB mRNA表达的检测，可在诊断及预后中发挥重要作用。【关键词】帕金森病；SIRT1/NF-κB信号通路；认知功能障碍；相关性；【中图分类号】R749

  关键词： 帕金森病；SIRT1/NF-κB信号通路；认知功能损害；相关性；; ; ; 

   

  Abstract: Correlation between SIRT1/NF-κB signaling pathway and cognitive impairment in patients with Parkinsons diseaseZHANG Lixia, LANG Zegao, WANG Hui Department of Neurology, Taizhou Second people’s Hospital,Taizhou 317200,Zhejiang,ChinaAbstractObjective: To study the correlation and diagnostic significance of the silent information regulator 2 related enzyme 1 (SIRT1)/nuclear factor kappa B (NF-κB) signaling pathway and cognitive impairment (CI) in patients with Parkinsons disease. Method: 119 patients with primary PD diagnosed and treated be in Taizhou Second people’s Hospital from September 2017 to March 2021 were selected as the PD group. According to the cognitive function status of the research subjects and related diagnosis guidelines, the included research subjects were divided into cognitive functions There were 33 cases in the normal subgroup (PD-NC), 58 cases in the mild cognitive impairment subgroup (PD-MCI), and 28 cases in the dementia subgroup (PDD).In addition, 50 healthy people who came to be in the hospital for physical examination during the same period were selected as the normal control group. After admission, the peripheral blood levels of SIRT1/NF-κB signaling pathway related molecules in all subjects were detected, and the relationship between the expression of SIRT1/NF-κB signaling pathway and cognitive function in PD patients was analyzed by partial correlation analysis. PD patients were secondary The analysis of the influencing factors of CI adopts Cox proportional hazard regression model analysis, and adopts receiver operating characteristic (ROC) curve to evaluate the diagnostic efficacy of SIRT1/NF-κB signaling pathway related molecule expression in PD patients with secondary CI.Results: There was a statistically significant difference between the two groups in terms of education level, course of disease, HY staging, UPDRS-Ⅲ, MoCA total score and other baseline data among different subgroups of PD patients (P<0.05); SIRT1 in PD group mRNA expression was significantly lower than that of the normal group, while NF-κB mRNA expression was higher than that of the normal group (P<0.05). The PD group was further stratified and compared, and it was found that the SIRT1 mRNA expression of the PDD group was significantly lower than that of the PD-MCI group The expression of the above indicators in the PD-NC group and PD-MCI group was also significantly lower than that in the PD-NC group (P<0.05), while the expression of NF-κB mRNA showed the opposite trend; using partial correlation analysis, SIRT1 and NF-κB mRNA were found There is still a significant correlation with MoCA score (r=0.637, -0.527, P<0.05);The results of Cox regression analysis showed that high H-Y staging and high expression of NF-κB mRNA were independent risk factors for the occurrence of CI in PD patients, and high expression of SIRT1 mRNA and high education level were independent protective factors for PD patients. The ROC curve showed that SIRT1 NF-κB mRNA expression can diagnose secondary CI in PD patients (P<0.05), and the two are fitted to predict. At this time, the AUC, sensitivity, and specificity are 0.875, 86.81%, and 90.36%, respectively. Conclusion: SIRT1 and NF-κB mRNA are highly expressed in the peripheral blood of patients with PD secondary to CI, and have a strong correlation with this type of cognitive function. Early enhancement of the detection of SIRT1 and NF-κB mRNA expression in peripheral blood of PD patients can be Play an important role in diagnosis and prognosis.Keywords Parkinsons disease; SIRT1/NF-κB signaling pathway; cognitive impairment; correlation;

  Key words: Parkinsons disease; SIRT1/NF-κB signaling pathway; cognitive impairment; correlation

  提交时间：2024-12-29

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  1	2024-10-23	bmr.202412.00077V1	下载

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