先天性心脏病相关性肺动脉高压患者血清高迁移率组蛋白B1变化及其临床意义

摘要

目的 探讨血清高迁移率组蛋白B1(HMGB1)作为先天性心脏病相关性肺动脉高压(CHD-PAH)患者生物标志物的可行性及临床价值.方法 收集2013年5月至2015年4月中南大学湘雅二医院CHD-PAH患者共83例,分为两个亚组,其中轻中度肺动脉高压组23例,重度肺动脉高压组60例,同时设置先天性心脏病未合并肺动脉高压组(23例)及健康成人对照组(20例).并对18例使用肺动脉高压靶向药物治疗的CHD-PAH患者随访6个月.采用酶联免疫法(ELISA)测定血清HMGB1质量浓度.结果 CHD-PAH患者血清HMGB1显著高于CHD未合并肺动脉高压组及健康对照组[(16.19±7.67)μg/L对5.35±2.03)μg/L;(16.19±7.67)μg/L对(3.76±1.25μg/L), P0.05];先心病合并重度肺动脉高压患者(A2)组HMGB1高于先心病合并轻中度肺动脉高压患者(A1)组,差异具有统计学意义[(19.12±6.70)μg/L对(8.54±3.71)μg/L,P0.05];先心病患者血清HMGB1与平均肺动脉压力、肺血管阻力呈显著正相关(r=0.864,r=0.593,P0.05);18例合并阻力型CHD-PAH患者使用肺动脉高压靶向药物治疗6个月后,在肺动脉压力和活动耐量得到改善的同时[(65.1±10.1) mmHg对(55.3±9.2) mmHg,P0.05],血清HMGB1显著降低[(18.12±5.31)μg/L对(13.51±1.47)μg/L,P0.05].结论 血清HMGB1可作为早期识别CHD-PAH患者的无创性筛查指标,可作为评估CHD-PAH患者肺血管重构的一种辅助手段,并在一定程度上反映肺动脉高压靶向药物的治疗效果.%Objective To estimate the clinical value of serum high mobility group box 1(HMGB1) as a biomarker of pulmonary arterial hypertension with congenital heart disease (CHD-PAH). Methods This study included 83 patients with pulmonary arterial hypertension associated with congenital heart disease in the Second Xiangya Hospital, Central South University from May 2013 to April 2015, and all the patients are divided into two groups according to mean pulmonary artery pressure(MPAP): congenital heart disease with mild-to-moderate pulmonary arterial hypertension group(group A1, n=23) and congenital heart disease with severe pulmonary arterial hypertension group(group A2, n=60). Then set two control groups: congenital heart disease without pulmonary arterial hypertension group(group B, n=23) and healthy adult control group(group C, n=20). Of all the patients with CHD-PAH, 18 were followed up for 6 months during treating with PAH-specific pharmacotherapies. All the subjects' clinical data were collected, cardiac catheterization and echocardiographs were performed. HMGB1 levels were determined by enzyme linked immunosorbent assay(ELISA). Results Serum HMGB1 levels were significantly increased in patients with CHD-PAH compared with CHD without PAH and control group(16.19±7.67 μg/L vs. 5.35±2.03 μg/L, 16.19±7.67 μg/L vs. 3.76±1.25 μg/L; P0.05); Serum HMGB1 levels were significantly increased in patients with mild-to-moderate CHD-PAH group compared with severe CHD-PAH group(19.12±6.70 μg/L vs. 8.54±3.71 μg/L, P0.05). The serum HMGB1 levels were significantly positive correlation with MPAP(r=0.864, P0.05) in patients with CHD. After treating with PAH-specific pharmacotherapies for 6 month, HMGB1 levels were significantly decreased(18.12±5.31 μg/L vs. 13.51±1.47 μg/L, P0.05) along with the patients' MPAP(65.1±10.1mmHg vs. 55.3±9.2 mmHg, P0.05) and six minutes walk distances improved. Conclution Our study suggested that serum HMGB1 may be used as a biomarker to identify CHD-PAH, to assess the pulmonary vascular remodeling in patients with PAH. Furthermore, HMGB1 level was a marker of treatment response to targeted therapy so that it has the potential to be used as a biomarker in the follow-up evaluation of patients with CHD-PAH.