妊娠糖尿病孕妇肠道菌群和炎症因子及T细胞亚群分析

Analysis of intestinal flora,inflammatory factors and T cell subsets in pregnant women with gestational diabetes mellitus

目的 妊娠糖尿病是女性妊娠期比较常见的疾病,探讨该类孕妇肠道菌群、炎症因子和T细胞亚群的关系以及对妊娠结局的影响。方法 选择2021年1月—2022年1月哈尔滨市第四医院收治的142名健康妊娠孕妇和74例妊娠糖尿病孕妇作为研究对象,分别纳入对照组和观察组。采用荧光定量聚合酶链反应(PCR)对全部孕妇肠道菌群(包括乳杆菌、肠杆菌、肠球菌、双歧杆菌、梭杆菌、拟杆菌)进行检测;应用酶联免疫吸附试验(ELISA)进行炎症因子[包括白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)]检测;应用流式细胞术对T细胞亚群(包括CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+))进行检测。应用Logistic多因素分析法针对妊娠糖尿病发生的相关危险因素进行分析;应用Spearman相关系数对肠道菌群、炎症因子、T细胞亚群与妊娠糖尿病孕妇妊娠结局的关系进行分析。结果 观察组孕妇的CRP、TNF-α、IL-2水平和肠球菌、梭杆菌、拟杆菌、肠杆菌数量均明显高于对照组,CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平和乳酸杆菌、双歧杆菌数量均明显低于对照组[CRP(g/L):6.86±1.03比4.15±0.96,TNF-α(μg/L):6.01±1.15比4.10±1.07,IL-2(ng/L):46.31±6.20比30.42±3.21,肠球菌(log N/g):8.51±0.66比7.53±0.61,梭杆菌(logN/g):3.65±0.08比3.05±0.06,肠杆菌(logN/g):10.03±0.70比8.13±0.72,拟杆菌(logN/g):9.21±0.52比8.05±0.46,CD3^(+):(0.68±0.07)%比(0.72±0.08)%,CD4^(+):(0.39±0.10)%比(0.45±0.12)%,CD4^(+)/CD8^(+):1.05±0.32比1.30±0.32,乳酸杆菌(logN/g):7.03±0.50比8.31±0.61,双歧杆菌(logN/g):6.96±0.45比8.85±0.50,均P<0.05]。观察组巨大儿、新生儿低血糖和剖宫产均明显多于对照组[巨大儿(例):10比6,新生儿低血糖(例):9比2,剖宫产(例):16比12,均P<0.05]。结论 针对妊娠糖尿病孕妇而言,肠道益生菌群数量有所减少,且机体免疫功能有所下降,炎症反应升高,同时肠道菌群、免疫功能及炎症反应的异常往往造成不良妊娠结局,及时采取相应干预措施可以有效降低妊娠糖尿病和不良妊娠结局的发生率。

Objective Gestational diabetes mellitus(GDM)is a common disease in pregnancy.This article aims to explore the relationship between intestinal flora,inflammatory factors and T cell subsets,and the impact on pregnant outcome.Methods The 142 healthy pregnant women and 74 pregnant women with GDM who were admitted to the Fourth Hospital of Harbin from January 2021 to January 2022 were selected as study subjects,and were respectively included in control group and observation group.The fluorescent quantitative polymerase chain reaction(PCR)was used to detect the intestinal flora(including Lactobacillus,Enterobacteriaceae,Enterococcus,Bifidobacterium,Fusobacterium and Bacteroides),the enzyme linked immunosorbent assay(ELISA)was used to detect inflammatory factors[including interleukin-2(IL-2),tumor necrosis factor-α(TNF-α)and C-reactive protein(CRP)],flow cytometry was used to detect T cell subsets(including CD3^(+),CD4^(+)and CD4^(+)/CD8^(+)).Through the application of Logistic multifactor analysis,the related risk factors of GDM were analyzed.Through the application of Spearman correlation coefficient,the relationship between intestinal flora,inflammatory factors,T cell subsets and the corresponding pregnancy outcome was analyzed.Results The levels of CRP,TNF-αand IL-2 and the number of Enterococcus,Fusobacterium,Bacteroides and Enterobacteriaceae in observation group were higher than those in control group,and the levels of CD3^(+),CD4^(+),CD4^(+)/CD8^(+)and the number of Lactobacilli and Bifidobacteria were lower than those in control group[CRP(g/L):6.86±1.03 vs.4.15±0.96,TNF-α(μg/L):6.01±1.15 vs.4.10±1.07,IL-2(ng/L):46.31±6.20 vs.30.42±3.21,Enterococcus(logN/g):8.51±0.66 vs.7.53±0.61,Fusobacterium(logN/g):3.65±0.08 vs.3.05±0.06,Enterobacteriaceae(logN/g):10.03±0.70 vs.8.13±0.72,Bacteroides(logN/g):9.21±0.52 vs.8.05±0.46,CD3^(+):(0.68±0.07)%vs.(0.72±0.08)%,CD4^(+):(0.39±0.10)%vs.(0.45±0.12)%,CD4^(+)/CD8^(+):1.05±0.32 vs.1.30±0.32,Lactobacillus(logN/g):7.03±0.50 vs.8.31±0.61,Bifidobacterium(logN/g):6.96±0.45 vs.8.85±0.50,all P<0.05].The observation group had more macrosomia,neonatal hypoglycemia and cesarean section compared to the control group[macrosomia(cases):10 vs.6,neonatal hypoglycemia(cases):9 vs.2,cesarean section(cases):16 vs.12,all P<0.05].Conclusions For pregnant women with GDM,the number of intestinal probiotics has decreased,the immune function has declined,and the inflammatory reaction has increased.At the same time,the abnormalities of intestinal flora,immune function and inflammatory reaction often lead to adverse pregnancy outcome.Timely taking appropriate intervention measures could effectively reduce the incidence of GDM and adverse pregnancy outcome.