内皮素、降钙素基因相关肽与先天性心脏病肺动脉压、肺血流量关系的研究

1、内皮素、降钙素基因相关肽与先天性心脏病肺动脉压、肺血流量关系的研究 2009-12-14 徐宝元李渝芬* 【摘要】目的探讨先天性心脏病(CHD)肺动脉高压(PH)的发病机理。方法采用非平衡放射免疫分析法测定52例肺高压(同伴Qp增加)和30例肺循环血流量(Qp)增加的先心病患儿上腔静脉(SVC)、右心房(RA)、右心室(RV)、肺动脉(PA)、肺静脉(PV)部位血浆ET-1浓度和SVC部位CGRP浓度，18例健康儿童作为对照。结果血浆ET-1浓度随着PH程度的加重和Qp的增加而升高，ET-1与肺动脉收缩压(SPAP)、全肺阻力(PVP)和Qp呈正相关(r=0.93,0.79,0.65;P0.0

2、1)，CGRP则相反(r=-0.90,-0.82, -0.55; P0.01)。SVC、RA、RV部位间ET-1浓度无显著差异(P0.05)，而RV、PA、PV间ET-1浓度都有显著差异(P0.01或0.05)。ET-1与CGRP呈负相关(r=-0.93,P0.01)。结论先心病PH和Qp增加皆可导致血浆ET-1浓度升高，PH时更著，升高之来源为肺循环。ET-1促进了先心病PH的形成和发展。Qp增加是PH形成的启动因子。CGRP的浓度下降和CGRP/ET-1的失衡可能是PH发病的另一因素。 【关键词】先天性心脏病内皮素-1降钙素基因相关肽肺动脉高压肺循环血流量 Correlations of

3、plasma endothelin-1 and calcitonin gene-related peptide concentrations to pulmonary arterial pressure and flow in children with congenital heart defects Xu Baoyuan, Li Yufen. Guangdong Provincial Cardiovascular Institute, Guangzhou 510100 【Abstract】ObjectiveTo study the pathogenesis of pulmonary hyp

4、ertension (PH) associated with congenital heart defects (CHD). MethodsPlasma endothelin-1 (ET-1) concentrations at superior vena cava (SVC), right atrium (RA), right ventricle (RV), pulmonary artery (PA) and pulmonary vein (PV), and calcitonin gene-related peptide (CGRP) concentration at SVC were me

5、asured by using the non-balanced radioimmunoassay in 52 patients with PH and 30 patients with the increased pulmonary blood flow (Qp) caused by CHD.ResultsThe plasma ET-1 concentrations elevated along with an increase in degree of PH and in Qp. ET-1 concentration correlated positively with systolic

6、pulmonary artery pressure (SPAP), total pulmonary resistance (PVR) and Qp(r=0.93, 0.79, 0.65; P0.01), respectively, while the plasma CGRP was correlated negatively with SPAP, PVR and Qp(r=-0.90,-0.82,-0.55; P0.01), respectively. There was no significant difference among SVC, RA and RV (P0.05), but w

7、ere significant differences among RV, PA and PV(P0.01 or P0.05). There was a negative correlation between ET and CGRP concentrations (r=-0.93, P0.01). ConclusionsPlasma ET-1 concentrations in patients with PH and increased Qp secondary to CHD are elevated, especially in patients with PH; the elevati

8、on is due to the increased production of ET-1 in pulmonary circulation. ET-1 promotes the formation and development of PH in patients with CHD, and is a major factor for the pathogenesis of PH. Increased Qp is also a factor inducing PH. Insufficient secretion of plasma CGRP and severe imbalance of C

9、GRP/ET-1 also were possiblely involved in the pathophysiology of PH. 【Key words】Congenital heart defects Endothelin-1 Calcionin geneRelated peptide Pulmonary hypertension Pulmonary blood flow 肺动脉高压(简称肺高压或PH)是先天性心脏病(简称先心病或CHD)常见并发症，是关系手术适应症及预后的重要因素之一，但其发病机理尚不清楚。内皮素-1(ET-1)是血管内皮细胞分泌的最强的缩血管肽1，而降钙素基因相关肽

10、(CGRP)则是肽能神经纤维释放的最强的舒血管肽2。本文探讨二者的消长变化及在PH发病中的意义。 对象和方法 一、研究对象 1.CHD组：82例，均为1998年2月1999年1月在我所住院的左向右分流型CHD患儿。其中男48例，女34例；年龄6个月14岁(4.8±3.6）岁。全部病例行心导管检查及选择性心血管造影确诊，包括室间隔缺损(VSD)47例，房间隔缺损(ASD)9例，动脉导管未闭(PDA)1例，ASD+VSD 4例，VSD+PDA 14例，ASD+PDA 1例，完全型房室隔缺损(CAVC)3例，部分型房室隔缺损(PAVC)2例，冠状动脉瘘(CAF)1例。全部病例均除外严重心律

11、失常、高血压、肺部感染及肝肾功能障碍等。 CHD组患儿分为肺高压组(PH组，52例)(同伴Qp的增加)和肺循环血量增加组(HQp组,30例)。PH组又分为三个亚组：轻度PH组，30 mmHg肺动脉收缩压(SPAP)50 mmHg(6.7 kPa),18例；中度PH组，50 mmHgSPAP70 mmHg(9.3 kPa),16例；重度PH组，SPAP70 mmHg，18例。HQp组又按肺/体循环血流量(Qp/Qs)分为两个亚组：少量左向右分流组(LF组)，Qp/Qs2.0， 15例；大量左向右分流组(HF组)，Qp/Qs2.0，15例。 PH组和HQp组之间，性别、年龄均相匹配，主动脉收缩压(

12、SABP)、Qs、体循环阻力(Rs)、体表面积、血红蛋白等均无显著差异。 2.对照组：18例，男10例，女8例，年龄8个月12.5岁(5.5±3.5）岁，均为健康体检者。 二、研究方法 1.血流动力学参数测定和计算：CHD组在右心导管检查中，经导管分别在上腔静脉(SVC)、下腔静脉(IVC)、右心房(RA)、右心室(RV)、肺动脉(PA)、肺静脉(PV)和主动脉(Ao)部位采血0.5 mL，用血氧分析仪测定这些部位血氧饱和度。同时接电生理记录仪测量右房平均压(MPAP)、SPAP、肺动脉平均压(MPAP)、SABP、主动脉平均压(MABP)。计算出血氧含量(mL/dL)、氧消耗量(mL/min),按Fick公式计算出QpL/（min.m2)、QsL/（min.m2)，继而算出Qp/Qs、全