早产儿血清mi R-125b,LncRNA MALAT1表达水平与支气管肺发育不良的相关性研究

Correlation between the Expression of Serum miR-125b,LncRNA MALAT1 and Bronchopulmonary Dysplasia in Premature Infants

目的 探讨早产儿血清微小核糖核酸(micro RNA,mi R)-125b,长链非编码RNA(long non-coding RNA,Lnc RNA)转移相关肺腺癌转录本-1(metastasis associated lung adenocarcinoma transcript 1,MALAT1)水平与支气管肺发育不良(broncho-pulmonary dysplasia,BPD)的关系。方法 选取2020年4月~2021年4月入住潍坊市妇幼保健院新生儿重症监护室(neonatal intensive care unit,NICU)的227例早产儿作为研究对象。采用实时荧光定量聚合酶链式反应(real-time quantitative polymerase chain reaction,RQ-PCR)检测血清mi R-125b和Lnc RNA MALAT1的表达水平;绘制血清mi R-125b和Lnc RNA MALAT1预测早产儿BPD发生的ROC曲线;多因素Logistic回归分析影响早产儿BPD的有关因素。结果 BPD组早产儿给氧时间34.54±9.21天,机械通气时间23.97±1.30h长于非BPD组(17.28±5.22天,4.71±2.26h),差异具有统计学意义(t=17.387,60.047,均P<0.05)。进入NICU后第10和14天,BPD组早产儿血清mi R-125b水平(0.70±0.18,0.48±0.16)均低于无BPD组(0.99±0.12,1.02±0.16),差异具有统计学意义(t=13.683,21.787,均P<0.05);血清Lnc RNAMALAT1水平(1.52±0.41,2.02±0.61)均高于无BPD组(1.03±0.15,1.02±0.11),差异具有统计学意义(t=13.198,20.569,均P<0.05);血清mi R-125b水平在轻度BPD组、中度BPD组和重度BPD组中依次降低(0.60±0.16,0.47±0.12,0.36±0.10),血清Lnc RNA MALAT1水平在轻度BPD组、中度BPD组和重度BPD组中依次升高(1.54±0.42,1.99±0.51,2.45±0.62),差异具有统计学意义(F=15.872,14.084,均P<0.05)。ROC分析结果显示,血清mi R-125b预测早产儿BPD的曲线下面积(AUC)为0.820(0.765~0.875),最佳诊断截点为0.59,Lnc RNA MALAT1预测早产儿BPD的AUC为0.773(0.685~0.861),最佳诊断截点为1.71,两个指标联合预测的价值最高,AUC为0.902(0.855~0.948)。多因素Logistic回归分析结果显示,给氧时间(OR:2.135,95%CI:1.241~3.674,P=0.006)、机械通气时间(OR:2.187,95%CI:1.132~4.225,P=0.020)和Lnc RNA MALAT1(OR:2.016,95%CI:1.190~3.416,P=0.009)是早产儿BPD的独立危险因素,mi R-125b(OR:0.699,95%CI:0.552~0.884,P=0.003)是早产儿BPD的独立保护因素。结论 血清mi R-125b水平降低及Lnc RNA MALAT1水平升高与早产儿BPD及严重程度有相关,检测早产儿血清mi R-125b,Lnc RNA MALAT1可为临床早期诊断治疗BPD提供理论依据。

Objective To investigate the relationship between serum micro RNA(miR)-125b,long non-coding RNA(LncRNA)metastasis associated lung adenocarcinoma transcript 1(MALAT1)levels and broncho-pulmonary dysplasia(BPD)in premature infants.Methods From April 2020 to April 2021,227 premature infants admitted to the neonatal intensive care unit(NICU)of Weifang Maternal and Child Health Hospital as the research objects.According to whether they have BPD or not,all preterm infants were divided into:BPD group(n=55)and non-BPD group(n=172).According to the inhaled oxygen concentration of premature infants,children in the BPD group were divided into mild BPD group(n=19),moderate BPD group(n=18)and severe BPD group(n=18).Real-time fluorescent quantitative PCR(qRT-PCR)method was used to detect the expression of serum miR-125b and LncRNA MALAT1 in all preterm infants.Using ROC curves to analyze the accuracy of serum miR-125b and LncRNA MALAT1 levels in predicting BPD in preterm infants,while identifying the optimal cutoff values for miR-125b and LncRNA MALAT1 in predicting BPD in preterm infants.Multivariate Logistic regression was used to analyze the related factors affecting BPD in premature infants.Results The oxygen administration time for premature infants in the BPD group was 34.54±9.21 days,and the mechanical ventilation time was 23.97±1.30 h,which was longer than that in the non BPD group(17.28±5.22 days,4.71±2.26 h),with statistically significant differences(t=17.387,60.047,all P<0.05).On the 10th and 14th days after entering NICU,the serum miR-125b levels of premature infants in the BPD group(0.70±0.18,0.48±0.16)were lower than those in the BPD group(0.99±0.12,1.02±0.16),with statistically significant differences(t=13.683,21.787,all P<0.05).The serum LncRNA MALAT1 levels(1.52±0.41,2.02±0.61)were higher than those in the BPD group(1.03±0.15,1.02±0.11),with statistically significant differences(t=13.198,20.569,all P<0.05).Serum miR-125b levels decreased sequentially in the mild BPD group,moderate BPD group and severe BPD group(0.60±0.16,0.47±0.12,0.36±0.10).Serum LncRNA MALAT1 levels increased sequentially in the mild BPD group,moderate BPD group and severe BPD group(1.54±0.42,1.99±0.51,2.45±0.62),with statistical significance(F=15.872,14.084,all P<0.05).The ROC analysis results showed that the area under the curve(AUC)of serum miR-125b for predicting BPD in preterm infants was 0.820(0.765~0.875),with an optimal diagnostic cutoff point of 0.59.The AUC of LncRNA MALAT1 for predicting BPD in preterm infants was 0.773(0.685~0.861),with an optimal diagnostic cutoff point of 1.71.The combination of the two indicators had the highest predictive value,with an AUC of 0.902(0.855~0.948).The results of multivariate logistic regression analysis showed that oxygen administration time(OR:2.135,95%CI:1.241~3.674,P=0.006),mechanical ventilation time(OR:2.187,95%CI:1.132~4.225,P=0.020),LncRNA MALAT1(OR:2.016,95%CI:1.190~3.416,P=0.009)were independent risk factors for premature BPD,and miR-125b(OR:0.699,95%CI:0.552~0.884,P=0.003)was an independent protective factor for premature BPD.Conclusion The decrease of serum miR-125b level and the increase of LncRNA MALAT1 level are related to BPD in premature infants,and both are related to the severity of BPD.The detection of serum miR-125b and LncRNA MALAT1 in premature infants can provide a theoretical basis for early clinical diagnosis and treatment of BPD.