小儿先天性心脏病并肺动脉高压血清基质金属蛋白酶与其组织抑制物的变化

Changes of serum MMP-2,MMP-9 and TIMP-1 in patients with congenital heart disease complicating pulmonary hypertension.

目的探讨先天性心脏病(先心病)患儿血清中的基质金属蛋白酶(MMP-2、MMP-9)、金属蛋白酶组织抑制物(TIMP-1)表达水平及其变化。方法2005年6月至2006年5月广西医科大学第一附属医院儿科收治左向右分流型先天性心脏病患儿81例,按治疗前肺动脉收缩压(SPAP)分为4组:非肺动脉高压(PH)组16例(SPAP<30mmHg),轻PH组21例(30mmHg≤SPAP<40mmHg),中PH组21例(40mmHg≤SPAP<70mmHg)和重PH组23例(SPAP≥70mmHg)。其中19例接受前列腺素E1(PGE1)治疗,24例接受手术治疗。对照组为21例为同龄正常体检儿。用酶联免疫吸附法(ELISA)检测血清MMP-2、MMP-9和TIMP-1含量,计算MMP-2/TIMP-1、MMP-9/TIMP-1。结果与对照组相比较,先心病各组MMP-2均显著增高;在各PH组MMP-9、TIMP-1均显著增高;在非PH、轻PH、中PH组MMP-2/TIMP-1均显著增高;在轻PH、中PH组MMP-9/TIMP-1显著增高。19例经PEG1治疗14d后,MMP-2、MMP-9和TIMP-1均显著下降。24例在手术治疗1周后,MMP-2、MMP-9、TIMP-1和MMP-2/TIMP-1均显著降低。结论(1)左向右分流型先心病血清存在MMP-2、MMP-9的显著增高,MMP-2、MMP-9可能协同参与肺血管重构,MMP-2对触发肺血管重构可能起着更积极的作用;(2)PGE1可有效降低先心病血清MMP-2、MMP-9和TIMP-1,这可能是PGE1逆转肺血管重构的机制之一;(3)介入封堵术和外科手术均可有效降低轻、中PH患儿血清MMP-2、MMP-9、TIMP-1和MMP-2/TIMP-1,其机制在于这两手术都阻断了先心病异常的血流动力学这一肺血管重构的始动因子。

Objective To explore the level and variation of serum matrix metalloproteinase（MMP-9,MMP-2） and metalloproteinase inhibition （ TIMP-1 ） in patients with congenital heart disease. Methods According to the preoperative pulmonary arterial systolic pressure （SPAP） ,81 patients with congenital heart disease were divided into four groups： no pulmonary hypertension （ PH ） group （ 16patients, SPAP 〈 30mmHg）, light PH group （ 21patients, 30mmHg ≤ SPAP 〈 40mmHg） ,moderate PH group （ 21patient, 40 mmHg ≤ SPAP 〈 70mmHg ） and heavy PH group （ 23patient, SPAP≥ 70mmHg）. 19 patients of them were comprehensively treated with PGE1.24 patients of the total patients were operated. The concentrations of serum MMP-9, MMP-2 and TIMP-1 were measured with ELISA. Then the rates of MMP-2/TIMP-1 and MMP-9/TIMP-1 were calculated. Results The concentrations of serum MMP-2 were increased remarkably in all groups of patients, compared with the control group. And the levels of MMP-9 and TIMP-1 were also significantly increased in all groups with PH. The rates of MMP-2/TIMP-1 were obviously increased in the non-PH group,light PH and moderate PH group. But there were obvious changes of the level of MMP-9/TIMP-1 in the light PH and moderate PH group. After 19 cases had been treated with PEG1 for 14 days, the levels of MMP- 9 ,MMP-2 and TIMP-1 were remarkably decreased. And after 7 days when 24 examples had received operation, the levels of serum of MMP-1, MMP-2,TIMP-1 and MMP-2/TIMP-1 were obviously decreased. Conclusion （ 1 ） The concentrations of set-um MMP-9,MMP-2 in patients with congenital heart disease of left-to-right shunt type obviously increase. They may synergistically contribute to the process of pulmonary vascular reconstitution and MMP-2 may be more positive in initiating pulmonary vascular reconstitution than MMP-9 does. （ 2 ） The concentrations of serum MMP-2, MMP-9 and TIMP-1 can be degraded obviously after the patients have been treated with PGE1 ,which may be one of the mechanisms that PGE1 can reverse pulmonary vascular remodeling. （3） The levels of serum MMP-9, MMP-2, TIMP-1 and MMP-2/TIMP-1 can also be degraded obviously after seven days of operations. Its mechanisms probably are that such operations can disrupt the abnormal hemodynamics of congenital heart disease, which is the initial factor that causes pulmonary vascular remodeling.