妊娠期糖尿病孕妇血清微小RNA-29a-3p、胰岛素样生长因子-1表达水平及其对胎儿生长受限的预测价值

Expression of serum microRNA-29a-3p and insulin-like growth factor 1 in pregnant women with gestational diabetes mellitus and its value in predicting fetal growth restriction

目的探究妊娠期糖尿病(GDM)孕妇血清微小核糖核苷酸(micro RNA,miR)-29a-3p、胰岛素样生长因子-1(IGF-1)表达水平及其对胎儿生长受限的预测价值。方法选择2019年8月—2022年12月在本院202例就诊分娩的GDM患者(132例)及同期体检健康孕妇(70名)作为研究对象,就诊分娩的GDM患者为患病组,同期体检健康孕妇为对照组。根据GDM患者是否伴有胎儿生长受限分为GDM组和胎儿生长受限组,GDM组88例,胎儿生长受限组44例。qRT-PCR法检测血清miR-29a-3p水平,放射免疫法检测血清IGF-1表达。TargetScanHuman网站预测miR-29a-3p与IGF-1靶向关系。分析miR-29a-3p、IGF-1及其与胰岛素水平、新生儿体重、新生儿身长的相关性;Logistic回归分析GDM孕妇发生胎儿生长受限的影响因素;ROC曲线分析血清miR-29a-3p,IGF-1水平评估GDM孕妇发生胎儿生长受限的预测价值。结果患病组孕妇血清miR-29a-3p水平高于对照组,IGF-1水平低于对照组,差异有统计学意义(P<0.05);GDM组患者血清miR-29a-3p水平低于胎儿生长受限组,IGF-1水平高于胎儿生长受限组,差异有统计学意义(P<0.05);miR-29a-3p直接靶向作用于IGF-1表达;GDM组和胎儿生长受限组孕妇胰岛素、新生儿体重、新生儿身长比较,差异具有统计学意义(P<0.05)。相关性分析表明,血清miR-29a-3p与IGF-1水平呈负相关(r=-0.402,P<0.05);血清miR-29a-3p水平与新生儿体重、新生儿身长呈负相关,IGF-1与新生儿体重、新生儿身长呈正相关(P<0.05)。Logistic回归分析表明,miR-29a-3p,IGF-1是GDM孕妇发生胎儿生长受限的影响因素(P<0.05)。血清miR-29a-3p,IGF-1水平联合评估GDM孕妇发生胎儿生长受限的曲线下面积(AUC)为0.877(95%CI:0.808-0.928),显著高于两指标单独检测(Z_(miR-29a-3p-联合)=2.893,P=0.004;Z_(IGF-1-联合)=2.810,P=0.005)。结论GDM孕妇血清miR-29a-3p水平上调,IGF-1水平下调,与胎儿生长受限密切相关,二者联合对GDM孕妇发生胎儿生长受限有较好预测价值。

Objective To investigate the expression levels of serum microRNA(miR)-29a-3p,insulin-like growth factor 1(IGF-1)in pregnant women with gestational diabetes mellitus(GDM)and its predictive value for fetal growth restriction.Methods The GDM pregnant women who got treatment and delivered in our hospital from August 2019 to December 2022 and health pregnant women receiving pregnancy examination in our hospital during the same period were enrolled as study subjects(202 women in total).The 132 GDM pregnant patients were collected as the diseased group,and the health pregnant women were enrolled in the control group.GDM pregnant patients were divided into GDM group and fetal growth restriction group based on presence and absence of fetal growth restriction,88 cases in GDM group and 44 cases in fetal growth restriction group.qRT-PCR method was applied to detect serum miR-29a-3p level,and radioimmunoassay was applied to detect IGF-1 expression in serum.TargetScanHuman website was applied to predict the targeting relationship between miR-29a-3p and IGF-1.The correlation between miR-29a-3p,IGF-1 and insulin levels,neonatal weight,and neonatal length was analyzed.Logistic regression was applied to analyze the influencing factors of fetal growth restriction in GDM pregnant women.Receiver operating characteristic was applied to analyze the value of serum miR-29a-3p and IGF-1 levels evaluation in predicting fetal growth restriction in GDM pregnant women.Results The serum miR-29a-3p of GDM pregnant women was obviously higher than that of healthy pregnant women,while the IGF-1 level was obviously lower than that of healthy pregnant women(P<0.05).The serum miR-29a-3p level in the GDM group was obviously lower than that in the fetal growth restriction group,while the IGF-1 level was obviously higher than that in the fetal growth restriction group(P<0.05).miR-29a-3p directly target IGF-1 expression.There were obvious differences in insulin level,neonatal weight,and neonatal length between the GDM group and the fetal growth restriction group(P<0.05).Correlation analysis showed a negative correlation between serum miR-29a-3p and IGF-1 levels(r=-0.402,P<0.05);the serum miR-29a-3p level was negatively correlated with neonatal weight and length,while IGF-1 was positively correlated with neonatal weight and length(P<0.05).Logistic regression analysis showed that miR-29a-3p and IGF-1 were the influencing factors for fetal growth restriction in GDM pregnant women(P<0.05).The area under the curve(AUC)of combined assessment of serum miR-29a-3p and IGF-1 levels for fetal growth restriction in GDM pregnant women was 0.877(95%CI:0.808-0.928),which was obviously higher than the two indicators tested separately(Z_(miR-29a-3p-combination)=2.893,P=0.004;Z_(IGF-1-combination)=2.810,P=0.005).Conclusions The miR-29a-3p level is up-regulated in GDM pregnant women,while IGF-1 level is down-regulated,they are closely related to fetal growth restriction.The combination of the two has good predictive value for fetal growth restriction in GDM pregnant women.