通过脑肠轴血清代谢物评估老年人认知功能的可行性研究  

Assessment of cognitive function of the elderly by serum metabolites of brain-gut axis

作　　者：吴铸 周起 李颖[2] 张楠[1] 刘恒硕 陈晨 庞国防[3] 梁庆华[3] 胡才友[3] 原慧萍[1] 杨泽[1] 孙亮[1] Wu Zhu;Zhou Qi;Li Ying;Zhang Nan;Liu Hengshuo;Chen Chen;Pang Guofang;Liang Qinghua;Hu Caiyou;Yuan Huiping;Yang Ze;Sun Liang(The Key Laboratory of Geriatrics,Beijing Institute of Geriatrics,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing Hospital/National Center of Gerontology of National Health Commission,P.R.China,Beijing 100730,China;Department of Geriatrics,the First Affiliated Hospital of Kunming Medical University,Kunming 650032,China;Department of Neurology,Guangxi Zhuang Autonomous Region Jiangbin Hospital,Nanning 530021,China)

机构地区：[1]北京医院,国家老年医学中心,国家卫生健康委北京老年医学研究所,国家卫生健康委老年医学重点实验室,中国医学科学院老年医学研究院,北京100730 [2]昆明医科大学第一附属医院老年病科,昆明650032 [3]广西壮族自治区江滨医院神经内科,南宁530021

出　　处：《中华医学杂志》2022年第2期125-129,共5页National Medical Journal of China

基　　金：国家自然科学基金(81571385,91849132);云南省科技厅昆明医科大学应用基础研究联合专项(202001AY070001-011);北京医院科技新星项目(BJ-2018-139);中国医学科学院青年医学人才奖励(2018RC330003);中国医学科学院医学与健康科技创新工程(2018-I2M-1-002)。

摘　　要：目的探讨通过脑肠轴血清代谢物评估老年人认知功能的可行性。方法采用方便抽样从2019年7月至10月间参加体检的健康人群队列和广西长寿人群微生态平衡队列中分别选取100和60名研究对象,构成健康人群子集和长寿人群子集。问卷调查收集人口学特征,采集空腹静脉血2~5 ml,采用液相色谱串联质谱技术进行血清非靶向代谢组学测定,通过文献检索汇总脑肠轴相关生物标志物,与非靶向代谢物测定结果取交集并进行注释。采用Spearman相关分析筛选与增龄相关的脑肠轴血清代谢物,采用多重线性回归法构建生物学年龄模型;采用简易精神状态检查表评估长寿人群子集认知功能,比较长寿人群子集不同认知功能老年人生物学年龄和时序年龄的差异。结果健康人群子集和长寿人群子集年龄的M(Q_(1),Q_(3))分别为64(38,72)和97(95,99)岁,女性分别为50(50.0%)和44名(73.3%)。初筛得到9种脑肠轴血清代谢物,分别为丙酸、谷氨酸、γ-氨基丁酸(GABA)、乳酸、5-羟色胺(5-HT)、色氨酸、氧化三甲胺、多巴胺和犬尿素。Spearman相关分析显示:谷氨酸和多巴胺与增龄呈正相关(r值分别为0.208和0.524,均P<0.05),色氨酸、5-HT和GABA与增龄呈负相关(r值分别为-0.308、-0.533和-0.213,均P<0.05)。构建生物学年龄模型为:y=49.81-1.18×10^(-5)×GABA-1.82×10^(-4)×5-HT+1.99×10^(-3)×多巴胺+1.65×10^(-6)×谷氨酸-2.04×10^(-6)×色氨酸+2.36×性别,式中:y为生物学年龄(岁),右侧各项依次为截距项、各代谢物相对水平和性别(男性=1,女性=2),模型的决定系数为0.50(P<0.001)。长寿人群子集认知功能较差、一般和较好者时序年龄的M(Q_(1),Q_(3))分别为97(94,100)、97(93,101)和96(94,101)岁,两两比较差异均无统计学意义(均P>0.05),认知功能较好的研究对象生物学年龄的M(Q_(1),Q_(3))为51(38,54)岁,低于认知功能较差者[57(47,61)](P=0.040)。结论可基于脑肠轴血清代谢物Objective To investigate the feasibility of assessing cognitive function of the elderly by serum metabolites of brain-gut axis.Methods Convenience sampling was used to select 100 and 60 participants from the healthy population cohort and microecological balance cohort of the longevity population in Guangxi,to constitute subset of healthy population and longevity population,respectively.A questionnaire was used to investigate the demographic characteristics of the subjects,2-5 ml of fasting venous blood was collected from the subjects,and the serum untargeted metabolomics was determined by liquid chromatography tandem mass spectrometry.The biomarkers related to the brain-gut axis were collected through literature retrieval,and the results were intersected with the untargeted metabolites and annotated.Spearman correlation analysis was used to screen serum metabolites of brain-gut axis associated with aging,and multiple linear regression method was used to construct biological age model.The mini mental status examination was used to evaluate the cognitive function of longevity population subsets.The differences of biological age and chronological age of longevity population subsets with different cognitive function were compared.Results The M(Q_(1),Q_(3))of subset of healthy population and longevity population were 64(38,72)and 97(95,99)years old,respectively,and there were 50(50.0%)and 44(73.3%)females,respectively.Nine serum metabolites of brain-gut axis were obtained by initial screening,which were propionic acid,glutamic acid,γ-aminobutyric acid(GABA),lactic acid,5-hydroxytryptamine(5-HT),tryptophan,trimethylamine oxide,dopamine and canine urea.Spearman correlation analysis showed that glutamic acid and dopamine were positively correlated with aging(r values were 0.208 and 0.524,respectively,all P values<0.05),and tryptophan,5-HT and GABA were negatively correlated with aging(r values were-0.308,-0.533 and-0.213,respectively,all P values<0.05).The biological age model was constructed as:y=49.81-1.18×10^(-5)×G

关 键 词：老年人 认知 代谢组 脑肠轴 生物学年龄 

分 类 号：R749.1[医药卫生—神经病学与精神病学]