摘要
目的探究阿尔茨海默病(AD)患者外周血淋巴细胞亚群与肠道菌群及认知损害的相关性。方法选取2021年10月至2023年10月收治的98例AD患者为AD组,根据病情严重程度再分为轻度组(27例)、中度组(51例)和重度组(20例);另选取同期健康体检者98例为对照组。采用流式细胞仪检测外周血淋巴细胞亚群;MicroScan微生物鉴定分析系统分析肠道菌群;简易精神状态检查量表(MMSE)和蒙特利尔认知评估(MoCA)量表评估认知功能。Pearson法和Spearman分析AD患者外周血淋巴细胞亚群与肠道菌群及认知损害的相关性;多因素Logistic回归分析AD的影响因素,利用系数乘积法进行中介效应分析。结果AD组外周血CD4^(+)、CD4^(+)/CD8^(+)、Treg和Treg/Th17水平显著低于对照组(均P<0.001),CD8^(+)和Th17水平显著高于对照组(均P<0.001)。轻度、中度和重度组外周血CD4^(+)、CD4^(+)/CD8^(+)、Treg和Treg/Th17水平依次降低(均P<0.05),CD8^(+)和Th17水平依次升高(均P<0.05)。轻度、中度和重度组双歧杆菌和乳酸杆菌依次降低(均P<0.05),肠杆菌、肠球菌和大肠埃希菌依次升高(均P<0.05)。Pearson和Spearman相关性分析提示,CD4^(+)、CD4^(+)/CD8^(+)、Treg以及Treg/Th17与双歧杆菌、乳酸杆菌以及MMSE、MoCA量表评分呈正相关(均P<0.001),与肠杆菌、肠球菌和大肠埃希菌呈负相关(P<0.05)。CD8^(+)和Th17与双歧杆菌、乳酸杆菌和MMSE、MoCA量表评分呈负相关(P<0.05),与肠杆菌、肠球菌和大肠埃希菌呈正相关(P<0.05)。多因素Logistic回归分析提示CD4^(+)、CD4^(+)/CD8^(+)、Treg、Treg/Th17、双歧杆菌、乳酸杆菌为AD的保护因素(P<0.05),CD8^(+)、Th17、肠杆菌、肠球菌和大肠埃希菌是AD的危险因素(P<0.05)。中介效应显示在较低的淋巴细胞亚群和肠道菌群关联中,有32.6%效应占比是通过肠道菌群来完成的。结论外周血淋巴细胞亚群CD4^(+)、CD4^(+)/CD8^(+)、Treg以及Treg/Th17在AD患者中显著降低,CD8^(+)和Th17显著升高,淋巴细胞亚群与肠道菌群及认知损害有关。
Aim To explore the correlation between peripheral blood lymphocyte subsets with gut microbiota and cognitive impairment in patients with Alzheimer’s disease(AD).Methods Ninety-eight patients with AD admitted to our hospital from October 2021 to October 2023 were selected as a AD group,and the patients were divided into a mild group(27 cases),a moderate group(51 cases)and a severe group(20 cases)according to the severity of the disease,and another 98 cases of those who had health checkups in our hospital during the same period were selected as the control group.Flow cytometry was applied to detect peripheral blood lymphocyte subsets.MicroScan microbial identification analysis system was applied to analyze the gut microbiota.Cognitive function assessment was conducted using the Mini-mental State Examination(MMSE)and Montreal Cognitive Assessment Scale(MoCA)scores.Pearson’s method and Spearman’s method were applied to analyze the correlation between peripheral blood lymphocyte subsets,gut microbiota,and cognitive impairment in AD patients.Multivariate Logistic regression was applied to analyze the factors affecting AD,and the intermediation effects was analyzed by coefficient product method.Results Peripheral blood CD4^(+),CD4^(+)/CD8^(+),Treg,and Treg/Th17 were significantly lower in the AD group than in the control group(all P<0.001),and CD8^(+)and Th17 were significantly higher than in the control group(all P<0.001).The levels of CD4^(+),CD4^(+)/CD8^(+),Treg and Treg/Th17 in peripheral blood of mild,moderate and severe groups were decreased successively(all P<0.05),while the levels of CD8^(+)and Th17 were increased successively(all P<0.05).The levels of bifidobacterium and lactobacillus decreased sequentially in the mild,moderate,and severe groups(all P<0.05),while enterobacterium,enterococcus,and escherichia coli increased sequentially(all P<0.05).According to Pearson and Spearman correlation analysis,CD4^(+),CD4^(+)/CD8^(+),Treg,and Treg/Th17 were positively correlated with bifidobacterium,lactobacillus,MMSE score,and MoCA score(P<0.001),and negatively correlated with escherichia coli,enterococcus,and escherichia coli(P<0.05).CD8^(+)and Th17 were negatively correlated with bifidobacterium,lactobacillus,MMSE and MoCA scores(P<0.05),and positively correlated with escherichia coli,enterococcus,and escherichia coli(P<0.05).Multivariate Logistic regression analysis showed that CD4^(+),CD4^(+)/CD8^(+),Treg,Treg/Th17,bifidobacterium,and lactobacillus were protective factors affecting AD(P<0.05),while CD8^(+),Th17,enterobacterium,enterococcus,and escherichia coli were risk factors affecting AD(P<0.05).Mediating effects showed a 32.6%effect share in lower lymphocyte subpopulation and gut flora associations through gut flora.Conclusion Peripheral blood lymphocyte subsets CD4^(+),CD4^(+)/CD8^(+),Treg,and Treg/Th17 are obviously reduced in AD patients,while CD8^(+)and Th17 are obviously increased.The lymphocyte subsets are associated with gut microbiota and cognitive impairment.
作者
常琳
章隽
高永红
CHANG Lin;ZHANG Jun;GAO Yong hong(Department of Cadre Medicine,Beijing Aerospace General Hospital,Beijing 100076,China)
出处
《中国临床神经科学》
2025年第2期176-182,共7页
Chinese Journal of Clinical Neurosciences
基金
中国航天科技集团公司第一研究院技术创新项目(编号:YC201801)。
关键词
阿尔茨海默病
淋巴细胞亚群
肠道菌群
认知损害
相关性
Alzheimer’s disease
lymphocyte subpopulations
gut microbiota
cognitive function
correlation
