载脂蛋白E基因型对急性大动脉粥样硬化性脑卒中血清炎症水平影响  

The impact of ApoE genotypes on serum levels of inflammatory cytokines in acute large-artery atherosclerosis stroke

作　　者：田冰洁 殷令妮 张寅飞 TIAN Bingjie;YIN Lingni;ZHANG Yinfei(Department of Geriatrics,Jiading District Central Hospital Affiliated Shanghai University of Medicine&Health Sciences,Shanghai,201800,China)

机构地区：[1]上海健康医学院附属嘉定区中心医院老年病科,上海201800

出　　处：《安徽医药》2023年第1期153-159,共7页Anhui Medical and Pharmaceutical Journal

摘　　要：目的研究载脂蛋白E(ApoE)基因型与急性大动脉粥样硬化性脑卒中相关性及其对血清炎症水平的影响。方法入组2018年10月至2020年5月上海健康医学院附属嘉定区中心医院收住首次急性缺血性脑卒中病人80例(起病<7 d),以及健康对照组74人。卒中组按照NIHSS评分,分为轻(≤3分)、中(4~11分)、重(≥12分)三组。按照梗死灶体积,分为小梗死组(<5 cm^(3))、中梗死组(5~15 cm^(3))、大梗死组(>15 cm^(3))。基因测序检测ApoE基因型,Luminex检测血清白细胞介素(IL)-1β(IL-1β)、IL-2、IL-4、IL-6、IL-10、IL-12p70、IL-17a、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)水平。Stata10进行统计分析,双侧(P<0.05)认为差异有统计学意义。结果与对照组相比,大动脉粥样硬化性脑卒中组中ApoEε3/ε4基因型(P=0.035)和等位基因ApoEε4比例(P=0.031)显著较高。logistic逐步回归矫正诸多混杂因素影响后,ApoEε4与大动脉粥样硬化性脑卒中仍显著相关;急性大动脉粥样硬化性脑卒中组血清IL-1β、IL-6、TNF-α水平显著高于健康对照组,IL-10显著低于α水平,大梗死组呈现较高的IL-1β、IL-12p70、TNF-α水平。卒中组中ApoEε4+人群血清IL-6水平(25.88±5.58)ng/L,显著高于ApoEε3/ε3(12.39±3.00)ng/L(P=0.024);IL-12p70水平(2.16±0.68)ng/L高于ApoEε3/ε3(1.05±0.22)ng/L(P=0.04);TNF-α水平(8.15±1.72)ng/L显著高于ApoEε2+(2.01±0.42)ng/L(P=0.012);而ApoEε4+(1.28±0.14)ng/L和ApoEε3/ε3(1.34±0.22)ng/L的IL-10水平则显著低于ApoEε2+(2.34±0.31)ng/L(P=0.001、0.038)。结论ApoEε4是大动脉粥样硬化性脑卒中重要的危险因素,ApoEε4携带卒中人群呈现较高炎症水平,表明ApoE可能通过参与炎症应答在缺血性脑卒中病理进程中发挥重要作用。Objective To explore the relevance between ApoE genotypes and acute large-artery atherosclerosis(LAA)stroke,as well as serum levels of inflammatory cytokines.Methods A total of 80 patients of first-ever acute LAA stroke(≤7 days)admitted to Ji‐ading District Central Hospital Affiliated Shanghai University of Medicine&Health Sciences from October 1,2018 to May 31,2020 and 74 controls were recruited in the study.According to the scores of National Institutes of Health Stroke Scale(NIHSS),the stroke group were further divided into mild defect group(≤3),moderate defect group(4-11)and severe defect group(≥12).According to the in‐farction volume,the stroke group were further divided into small infarction group(<5cm^(3)),medium infarction group(5-15 cm^(3))and large infarction group(>15cm^(3)).Gene sequencing was performed to analyze ApoE genotypes.The following inflammatory cytokines were measured by Luminex:IL-1β,IL-2,IL-4,IL-6,IL-10,IL-12p70,IL-17a,IFN-γ,TNF-α.Stata 10 software package was used for statistical analysis.Two-sided(P<0.05)was considered statistically significant.Results Compared with the control group,the propor‐tion of genotype ApoEε3/ε4(P=0.035)and allele ApoEε4(P=0.031)were significantly higher in LAA group;In a stepwise logistic re‐gression analysis after adjustment for numerous confounding factors,the associations between ApoEε4 and LAA stroke remained signif‐icant;The serum levels of the IL-1β,IL-6 and TNF-αwere significantly higher in acute LAA patients than in the controls,while IL-10 levels were significantly lower in patients(P=0.038).Patients of severe defect group showed higher levels of IL-1β,IL-6 and TNF-α.Patients of large infarction group showed higher levels of IL-1β,IL-12p70 and TNF-α;In stroke patients,the IL-6 levels were signifi‐cantly higher in ApoEε4+group(25.88±5.58)ng/L than in ApoEε3/ε3 group(12.39±3.00)ng/L,(P=0.024);the IL-12p70 levels were significantly higher in ApoEε4+group(2.16±0.68)ng/L than in ApoEε3/ε3 group(1.05±0.22)ng/L,(P=0.0

关 键 词：脑梗死 载脂蛋白E类 白细胞介素类 肿瘤坏死因子α 缺血性卒中 神经炎症 

分 类 号：R743.3[医药卫生—神经病学与精神病学]