脑梗死和短暂性脑缺血患者肠道菌群、血清载脂蛋白E水平变化及其相关性

Change of intestinal microbiota and apolipoprotein E in cerebral infarction and transient ischemic attack patients and their correlation

目的观察脑梗死和短暂性脑缺血患者肠道菌群变化,分析其与血清载脂蛋白E(apolipoprotein E,ApoE)的相关性。方法留取脑梗死(30例,脑梗死组)和短暂性脑缺血(30例,短暂性脑缺血组)患者发病24 h内的粪便标本、血清标本,以健康志愿者(30例,健康组)的粪便标本、血清标本作对照。采用16s测序技术观察受检者粪便标本肠道菌群丰度变化并分析其特征。ELISA检测血清ApoE。对肠道菌群相对丰度与血清ApoE水平进行相关性分析。结果与健康组相比,脑梗死组肠道菌群中的拟杆菌门、疣微菌门、放线菌门、蓝藻门、互养菌门和浮霉菌门相对丰度显著降低(P<0.05),短暂性脑缺血组肠道菌群中的软壁菌门和放线菌门相对丰度显著升高(P<0.05),疣微菌门、蓝藻门、互养菌门和浮霉菌门相对丰度显著降低(P<0.05);与短暂性脑缺血组相比,脑梗死肠道菌群中的厚壁菌门相对丰度显著升高(P<0.05),拟杆菌门、疣微菌门、软壁菌门、放线菌门、蓝藻门和浮霉菌门相对丰度显著降低(P<0.05)。健康组和脑梗死组肠道菌群群落结构具有显著异质性(胁迫系数stress<0.05,P<0.05);脑梗死组肠道菌群微生物多样性显著低于健康组和短暂性脑缺血组(P<0.05)。脑梗死组血清ApoE水平显著高于短暂性脑缺血组和健康组(P均<0.05),分别为(36.2±6.3)、(33.2±5.4)、(32.8±5.7)mg/L。肠道菌群中的拟杆菌门相对丰度与血清ApoE水平呈负相关(r=-0.606 8,P<0.05)。结论脑梗死和短暂性脑缺血患者存在肠道菌群紊乱现象,肠道拟杆菌门相对丰度与ApoE水平有关,肠道菌群紊乱可能是脑缺血疾病的潜在致病因素。

Objective To investigate the alteration of intestinal microbiota of cerebral infarction(CI)and transient ischemic attack(TIA)patients,and to analyze its correlation with apolipoprotein E(ApoE).Methods The fecal samples from 30 cases of healthy subjects(healthy group),30 cases of TIA patients(TIA group)and 30 cases of CI patients(CI group)within 24 h were determined by 16s sequencing technology for structural and characteristic analysis.The level of ApoE of these subjects was measured by ELISA.The correlation between the relative abundance of bacteroidetes and ApoE was analyzed.Results Compared with healthy group,the abundances of Bacteroidetes,Verrucomicrobia,Actinobacteria,Cyanobacteria,Synergistetes and Planctomycetes decreased in the CI group(all P<0.05),whereas the abundances of Tenericutes and Actinobacteria increased,and the abundances of Verrucomicrobia,Cyanobacteria,Synergistetes and Planctomycetes decreased in the TIA group(all P<0.05).Compared with the TIA group,Firmicutes increased,but Bacteroidetes,Verrucomicrobia,Tenericutes,Actinobacteria,Cyanobacteria,and Planctomycetes decreased in the CI group(all P<0.05).Non-metric multidimensional scaling(NMDS)analysis showed that there was a significant heterogeneity between healthy and CI groups in microbiota structure(stress<0.05,P<0.05).There was a decreased microbiota diversity by chao1 analysis and an increased ApoE level in the CI group[(36.2±6.2)mg/L]as compared with that of the health group[(32.8±5.7)mg/L]and TIA group[(33.2±5.4)mg/L](all P<0.05).However,there was no significant difference between healthy group and TIA group(P>0.05).There was negative correlation between Bacteroidetes and ApoE(r=-0.606 8,P<0.05).Conclusion There is a confusion in intestinal flora of CI and TIA patients,Bacteroidetes is related to ApoE level,and the intestinal flora disorder may be a potential cause of cerebral ischemic disease.