目的：探讨妊娠期糖尿病（GDM）女性循环miRNAs的差异表达,确定GDM相关的潜在分子标志物。方法：采集自2020年1月―2022年6月期间西北妇女儿童医院的53名GDM孕妇和30名年龄和孕周相匹配的正常孕妇的血浆样本。采用miRNA高通量测序筛选GDM相关的循环miRNA,实时定量PCR（RT-qPCR）验证。使用受试者工作特征（ROC）曲线评估循环miR-101-3p预测GDM的价值。采用酶联免疫吸附法测定血清hs-CRP、TNF-α水平。结果：与健康对照组相比,GDM组孕妇具有较高的甘油三酯、hs-CRP、TNF-α水平和较低的HDL-C水平。在检测的2549个血浆miRNA中,267个miRNA的表达在两组之间显示出2倍或更大的差异。PCR分析显示,与健康受试者相比,GDM孕妇的血浆miR-101-3p显著下调。KEGG途径富集发现,miR-101-3p可能参与葡萄糖、炎症调节和脂质的代谢。ROC曲线分析显示,miR-101-3p区分健康对照组和GDM组的敏感性为0.852,特异性为0.737,AUC值为0.845。相关性分析显示,血浆miR-101-3p的表达与血糖水平、hs-CRP、TNF-α呈显著负相关（r=-0.649、-0.602、-0.735,均P<0.001）。结论：miR-101-3p可能参与GDM患者的胰岛素抵抗和炎症因子调节。
Abstract
Objective To explore the differential expression of circulating miRNAs between healthy women and women with gestational diabetes mellitus (GDM), and to identify potential molecular markers related to GDM. Methods Plasma samples were taken from 53 pregnant women with GDM and 30 normal pregnant women with matched age and gestational weeks in Northwest Women's and Children's Hospital from January 2020 to June 2022. The miRNA high-throughput sequencing was used to screen circulating miRNAs related to GDM. Real-time quantitative PCR (RT-qPCR) was used to verify the differentially expressed candidate miRNAs identified from the mirna analysis experiment. Evaluating the expression level of circulating miR-101-3p by using receiver operating characteristic (ROC) curve to predict the value of GDM. Serum hs-CRP and TNF-α levels were measured by enzyme-linked immunosorbent assay. Results Compared with the healthy control group, pregnant women in GDM group had higher levels of triglyceride, hs-CRP, TNF-α and lower levels of HDL-C. Among the 2549 plasma mirnas detected, 267 mirnas showed 2 times or more difference in expression between the two groups. Enrichment of KEGG pathway revealed that miR-101-3p may be involved in glucose, inflammation regulation and lipid metabolism. PCR analysis showed that the plasma miR-101-3p of GDM pregnant women was significantly down-regulated compared with healthy subjects. ROC analysis showed that the sensitivity, specificity and AUC of miR-101-3p in distinguishing healthy control group from GDM group were 0.852, 0.737 and 0.845, respectively. Correlation analysis showed that the expression of plasma miR-101-3p was negatively correlated with blood glucose level, hs-CRP and TNF-α (r=-0.649, -0.602 and -0.735, all P<0.001). Conclusions MiR-101-3p may be involved in insulin resistance and the regulation of inflammatory factors in GDM patients.
关键词
妊娠期糖尿病 /
胰岛素抵抗 /
miRNAs /
炎症因子
Key words
gestational diabetes /
insulin resistance /
miRNAs /
inflammatory factor
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