文章摘要
田冰洁,殷令妮,张寅飞.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[J].安徽医药,2023,27(1):153-159.
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
  
DOI:10.3969/j.issn.1009-6469.2023.01.034
中文关键词: 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
英文关键词: Brain infarction  Apolipoproteins E  Interleukins  Tumor necrosis factor-alpha  Ischemic stroke  Neuroinflam mation
基金项目:
作者单位E-mail
田冰洁 上海健康医学院附属嘉定区中心医院老年病科上海 201800  
殷令妮 上海健康医学院附属嘉定区中心医院老年病科上海 201800  
张寅飞 上海健康医学院附属嘉定区中心医院老年病科上海 201800 jzxlnbk2018@yeah.net 
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中文摘要:
      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 cm3)、中梗死组( 5~15 cm3)、大梗死组( >15 cm3)。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 ApoE ε3/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。
英文摘要:
      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 Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences from October 1, 2018 to May 31, 2020and 74 controls were recruited in the study. According to the scores of National Institutes of Health Stroke Scale (NIHSS), the strokegroup were further divided into mild defect group (≤3), moderate defect group (4-11) and severe defect group (≥12). According to the infarction volume, the stroke group were further divided into small infarction group (<5cm3), medium infarction group (5-15 cm3) and large infarction group (>15cm3). Gene sequencing was performed to analyze ApoE genotypes. The following inflammatory cytokineswere 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 proportion of genotype ApoEε3/ε4 (P=0.035) and allele ApoEε4 (P=0.031) were significantly higher in LAA group; In a stepwise logistic regression analysis after adjustment for numerous confounding factors, the associations between ApoEε4 and LAA stroke remained significant ; The serum levels of the IL-1β, IL-6 and TNF-α were 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 significantly 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=0.049); the TNF-α levels were significantly higher in ApoEε4+ (8.15±1.72) ng/L group than in ApoEε2+ group (2.01±0.42) ng/L, (P=0.012). Compared with patients of ApoEε2+ (2.34±0.31) ng/L group, IL-10 levels were significantly lower in ApoEε4+ group (1.28±0.14) ng/L, (P=0.001) and ApoEε3/ ε3 group (1.34±0.22) ng/L(P=0.038). Conclusions ApoEε4 is an important risk factor for the large-artery atherosclerosis stroke.ApoEε4 carriers have a high level of inflammation, indicating that ApoE plays an important role in the pathological process of ischemic
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