摘要目的 分析补体因子H相关蛋白2(CFHR2)在先天性心脏病(CHD)相关的肺动脉高压(CHD-PAH)患儿血浆中的改变及临床意义.方法 收集66例CHD及CHD-PAH患儿样本,包括室间隔缺损并PAH(VSD-PAH) 11例、单纯VSD无PAH(VSD) 11例、房间隔缺损并PAH(ASD-PAH) 11例、单纯ASD无PAH(ASD) 11例、混合型心脏缺陷[即合并2种及2种以上的VSD、ASD及动脉导管未闭(PDA)疾病]并PAH(Mix-PAH) 11例、混合型心脏病缺陷无PAH(Mix) 11例,16例健康儿童作为健康对照组.应用酶联免疫吸附试验对各组血浆中CFHR2蛋白的表达进行验证.结果 与健康对照组血浆中CFHR2蛋白水平[(189.10±24.01)μg/L]相比,VSD-PAH组[(42.99±4.53) μg/L,t=4.975,P＜0.01]及VSD组[(165.00±23.17)μg/L,t=2.661,P＜0.05]显著下调;VSD-PAH组与VSD组血浆中CFHR2蛋白水平比较差异有统计学意义(t=4.698,P＜0.01).与健康对照组血浆中CFHR2蛋白水平相比,ASD-PAH组[(70.92±8.27) μg/L,t=3.951,P＜0.05]及ASD组[(72.48±8.99) μg/L,t=3.880,P＜0.01]显著下调;ASD-PAH组与ASD组比较差异无统计学意义(t=0.128,P＞0.05).与健康对照组相比,Mix-PAH组血浆中CFHR2蛋白水平[(83.23±15.96)μg/L,=3.314,P＜0.05]显著下调,而Mix组患儿血浆中CFHR2蛋白[(170.40±33.15) μg/L,t=0.468,P＞0.05]与健康对照组比较差异无统计学意义;Mix-PAH组与Mix组患儿CFHR2蛋白水平比较差异有统计学意义(t=2.370,P＜0.05).结论 CHD-PAH患儿血浆CFHR2蛋白减少可能与患儿免疫系统缺陷及其凝血系统障碍有关,该蛋白有可能成为CHD-PAH疾病的生物标志物之一.

abstractsObjective To detect the changes and the clinical significance in plasma protein-complement factor H-related protein 2 (CFHR2) in pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) children.Methods Various types of 66 CHD patients with or without PAH and 16 healthy children(healthy control group) were studied,including 11 ventricular septal defects (VSD) with PAH (VSD-PAH),11 isolated VSD,11 atrial septal defects with PAH (ASD-PAH),11 isolated ASD,11 mixed type of heart defects [two or more defects of VSD,ASD and patent ductus arteriosus (PDA)] with PAH (Mix-PAH) and 11 cases without PAH (Mix).CFHR2 was validated by enzyme linked immunosorbent assay in the sample plasma.Results Compared with the healthy control group,the CFHR2 concentration in VSD-PAH patients [(189.10 ±24.01) μg/L vs.(42.99 ±4.53) μg/L,t =4.975,P ＜0.01] and VSD patients [(189.10 ±24.01) μg/L vs.(165.00 ±23.17) μg/L,t =2.661,P ＜ 0.05] were lower.The CFHR2 protein was also confirmed to be decreasing significantly in VSD-PAH patients compared with VSD patients (t =4.698,P ＜ 0.01).The plasma CFHR2 level in ASD-PAH patients [(189.10 ± 24.01)μg/L vs.(70.92 ± 8.27) μg/L,t =3.951,P ＜0.01] and ASD patients [(189.10 ±24.01) μg/L vs.(72.48 ± 8.99) μg/L,t =3.880,P ＜ 0.01] were significantly lower than those in the healthy control group,although there was no significant difference between ASD-PAH and ASD patients (t =0.128,P ＞ 0.05).The plasma CFHR2 level in Mix-PAH patients [(189.10 ± 24.01) μg/L vs.(83.23 ± 15.96) μL,t =3.314,P ＜ 0.05] was significantly lower than that in the healthy control group,while Mix patients [(189.10 ±24.01) μg/L vs.(170.40 ±33.15) μg/L,t =0.468,P ＞ 0.05] had no difference compared with the healthy control group,but had statistical significance with M ix PAH group (t =2.370,P ＜ 0.05).Conclusions The decrease of CFHR2 protein may demonstrate the deficiency of the immune system and coagulation mechanism in these patients and can be consi-dered as biomarker of CHD-PAH disease.