特发性肺动脉高压患儿血清miR-182 和ICAM-1 表达水平及其与预后相关性分析

目的　探讨血清微小核糖核酸（micro RNA，miR）-182、细胞间黏附分子（intercellular adhesion molecule-1，ICAM）-1 在特发性肺动脉高压（idiopathic pulmonary arterial hypertension，IPAH）患儿中的表达及其预后预测价值。方法　选取2016 年6 月～ 2020 年12 月就诊于承德市妇幼保健院肺动脉高压中心的76 例IPAH 患儿为研究对象（观察组），另选取同期在医院进行体检的健康儿童30 例作为对照组，比较二组血清miR-182，ICAM-1 水平。收集IPAH 患儿常规实验室检查、心脏超声检查及心导管检查等资料，并进行随访，随访的终点事件定义为死亡或行肺移植治疗，根据患儿预后情况将其分为存活组和死亡组。采用Logistic 回归分析筛选影响IPAH 患儿预后的危险因素，绘制受试者工作特征（receiver operating characteristic，ROC）曲线评价血清miR-182，ICAM-1 单独及联合检测对IPAH 患儿预后的预测价值。结果　观察组血清miR-182（1.91±0.20），ICAM-1（305.67±32.46 ng/ml）水平均高于对照组（0.15±0.02，203.22±21.51 ng/ml），差异具有统计学意义（t=-73.624，-33.698，均P ＜ 0.05）。72 例患儿获得随访，其中死亡21 例（29.17%），存活51 例（70.83%）。死亡组NYHA 心功能分级（III ～ IV 级）占比、脑钠肽（brainnatriuretic peptide，BNP）、总胆红素（total bilirubin，TB）、红细胞分布宽度（red cell volume distribution width，RDW）、肺动脉收缩压（systolic pulmonary artery pressure，sPAP）、全肺阻力（total pulmonary resistance，TPR）、miR-182 和ICAM-1 水平均高于存活组，差异具有统计学意义（χ2=4.138，t’=-75.584，t=7.231，6.197，2.464，3.930，t’=6.782，3.328，均P ＜ 0.05）。NYHA 心功能分级（高级）（OR=1.681，95%CI=1.370 ～ 5.128），RDW（OR=2.112，95%CI=1.212 ～ 5.135），sPAP（OR=2.597，95%CI=1.052 ～ 6.1425），miR-182（OR=3.587，95%CI=1.249 ～ 6.125）和ICAM-1（OR=3.634，95%CI=1.135 ～ 5.153）是影响IPAH 患儿预后的危险因素（均P ＜ 0.05）。血清miR-182 和ICAM-1 预测IPAH 患儿预后的曲线下面积（AUC）分别为0.761，0.770，联合预测的AUC 为0.883，优于各指标单独预测（Z= -3.236，-3.211，均P ＜ 0.05）。结论　血清miR-182 和ICAM-1 在IPAH 患儿中呈现异常高表达，二者与患儿预后存在一定关系，在一定程度上可作为有效预测指标。

Analysis of Serum miR-182 and ICAM-1 Expression Levels in Children with Idiopathic Pulmonary Hypertension and Their Correlation with Prognosis

Objective　To investigate the expression of serum micro RNA（miR）-182 and intercellular adhesion molecule-1 (ICAM)-1 in children with idiopathic pulmonary arterial hypertension (IPAH) and their the prognostic value of ICAM-1 in children with idiopathic pulmonary arterial hypertension (IPAH). Methods　76 children with IPAH who attended the Pulmonary Hypertension Center of Chengde Maternal and Child Health Hospital from June 2016 to November 2020 were selected for the study (observation group), and another 30 healthy children who underwent physical examination at the hospital during the same period were selected as the control group to compare the serum miR-182 and ICAM-1 levels in the two groups. Routine laboratory tests, cardiac ultrasonography and cardiac catheterization were collected from children with IPAH and followed up with an endpoint event defined as death or undergoing lung transplantation, and the children were divided into survival and death groups according to their prognosis. Logistic regression analysis was used to screen the risk factors affecting the prognosis of children with IPAH, and receiver operating characteristic(ROC）curves were drawn to evaluate the individual and combined predictive value of serum miR-182 and ICAM-1 on the prognosis of children with IPAH. Results　The levels of serum miR-182 (1.91±0.20) and ICAM-1 levels (305.67±2.46 ng/ml) were higher in the observation group than in the control group (0.15±0.02, 203.22±21.51 ng/ml), and the differences were statistically significant (t=-73.624，-33.698, all P<0.05). 72 children were followed up, of which 21 (29.17%) died and 51 (70.83%) survived. The percentage of NYHA cardiac function class (III ～ IV) in the death group, brain natriuretic peptide (BNP), total bilirubin (TB), red blood cell distribution width (RDW), systolic pulmonary artery pressure (sPAP), total pulmonary resistance (TPR), miR-182 and ICAM-1 levels were higher than those in the survivor group, all with statistically significant differences ( χ2=4.138，t’=-75.584, t=7.231, 6.197, 2.464, 3.930, t’=6.783， 3.328, all P<0.05). NYHA cardiac function class (advanced) （OR=1.681，95%CI=1.370 ～ 5.128），RDW（OR=2.112， 95%CI=1.212 ～ 5.135），sPAP（OR=2.597，95%CI=1.052 ～ 6.1425），miR-182（OR=3.587，95%CI=1.249 ～ 6.125） and ICAM-1（OR=3.634，95%CI=1.135 ～ 5.153） were risk factors affecting the prognosis of children with IPAH (all P<0.05). The area under the curve (AUC) of serum miR-182, ICAM-1 to predict the prognosis of children with IPAH was 0.761 and 0.770, respectively, and the combined AUC was 0.883, which was better than each index alone (Z= -3.236，-3.211, all P<0.05). Conclusion　Serum miR-182 and ICAM-1 show abnormally high expression in children with IPAH, both of which would be related to the prognosis of the children and could be used as effective predictors to some extent.