老年人尿尼古丁代谢物与认知功能的关联及高同型半胱氨酸血症的中介作用  

Correlating urinary nicotine metabolites with cognitive function and the mediating effect of hyperhomocysteinemia in the elderly

作　　者：支赢 任晓虎[2] 黄嘉 吕媛[1] 梅鹏程 周琪嵋 王佳辉 刘建军 ZHI Ying;REN Xiaohu;HUANG Jia;LÜYuan;MEI Pengcheng;ZHOU Qimei;WANG Jiahui;LIU Jianjun(Key Laboratory of Molecular Epidemiology of Hunan Province,School of Medicine,Hunan Normal University,Changsha 410013,China;Shenzhen Key Laboratory of Modern Toxicology,Shenzhen Medical Key Discipline of Health Toxicology,Shenzhen Center for Disease Control and Prevention,Shenzhen 518055,China)

机构地区：[1]湖南师范大学医学院“分子流行病学”湖南省重点实验室,长沙410013 [2]深圳市疾病预防控制中心深圳市现代毒理学重点实验室,深圳市卫生毒理学医学重点学科,深圳518055

出　　处：《分析试验室》2025年第2期233-240,共8页Chinese Journal of Analysis Laboratory

基　　金：深圳市基础研究重点项目(JCYJ20200109143431341);深圳市医疗卫生三名工程项目(SZSM202211010);深圳市医学重点学科建设(SZXK069)资助。

摘　　要：本文探讨了尿中尼古丁代谢物与认知功能的关联以及高同型半胱氨酸血症(HHcy)在其中的中介作用。利用整群抽样的方法,从深圳市某社区抽取2010名60岁及以上本地居民作为研究对象,进行现场流行病学调查、健康体检和认知量表评估(Mini-cog)。采用高效液相色谱串联质谱法(HPLC-MS/MS)检测尿中10种尼古丁代谢物的浓度。用多因素条件逻辑回归(MLR)和弹性网络回归(ENR)模型研究了尿尼古丁代谢物与认知功能的关系,并分析了HHcy的中介作用。结果显示,教育水平与认知障碍风险呈负相关(P<0.05),吸烟史与认知障碍风险呈正相关(P<0.05)。此外,羟基可替宁糖苷(OHCotGluc)与认知功能障碍风险呈正向关联,可替宁(Cot)和烟碱糖苷(NicGluc)与认知障碍风险呈负向关联。HHcy介导OHCotGluc和NicGluc与认知功能障碍风险之间的关联有显著意义(P<0.05),中介效应分别占40.11%和37.67%。上述结果表明,高等教育水平以及较高浓度的Cot和NicGluc是认知障碍的保护因素,吸烟史和高浓度的OHCotGluc是认知障碍的独立危险因素,且HHcy在OHCotGluc和NicGluc与认知功能障碍关系中存在中介效应。To explore the association between urinary nicotine metabolites and cognitive function,and examine the mediating role of hyperhomocysteinemia(HHcy)in this relationship,a total of 2010 residents aged 60 and above were selected from a community in Shenzhen by cluster sampling.Field epidemiological investigation,physical examination,and cognitive assessment(Mini-cog)were conducted on the participants.The concentrations of 10 nicotine metabolites in urine were measured using high performance liquid chromatography-mass spectrometry(HPLC-MS/MS).The relationships between urinary nicotine metabolites and cognitive function were assessed through conditional Logistic regression(CNR)and Elastic-Net Regression(ENR)models,with additional analysis for the mediating role of HHcy.The results indicated that education level was negatively associated with risk of cognitive impairment(P<0.05),while smoking history was positively correlated with the risk of cognitive impairment(P<0.05).In addition,trans-3'-hydroxy cotinine O-β-D-glucuronide(OHCotGluc)was positively associated with cognitive dysfunction,while cotinine(Cot)and nicotine-N-β-glucuronide(NicGluc)were negatively associated with cognitive dysfunction.HHcy was found to mediate a significant association between OHCotGluc and NicGluc,and the risk of cognitive dysfunction(P<0.05)with a mediating effect of 40.11%and 37.67%.The above results showed that a relatively high level of education and elevated concentrations of Cot and NicGluc serve as protective factors against the risk of cognitive impairment.Conversely,smoking history and OHCotGluc act as risk factors for cognitive dysfunction.Furthermore,HHcy was identified as mediating the relationship between OHCotGluc,NicGluc and cognitive function.

关 键 词：尿尼古丁代谢物 认知功能障碍 老年人体检 高同型半胱氨酸血症 

分 类 号：R122.7[医药卫生—环境卫生学] R749.1[医药卫生—公共卫生与预防医学]