基质金属蛋白酶-2及其抑制物与血管内皮生长因子在小儿先天性心脏病不同肺动脉压力情况下的变化  

Role of serum MMP-2,TIMP-1 and VEGF in pulmonary vascular reconstitution in patients with congenital heart disease

作　　者：曾红军 庞玉生[2] 梁秀安[2] 陈玉君[2] 

机构地区：[1]广西柳州市妇幼保健院儿科,广西柳州545001 [2]广西医科大学第一附属医院儿科,广西南宁530021

出　　处：《心脏杂志》2010年第2期205-208,共4页Chinese Heart Journal

基　　金：广西回国人员科学基金课题项目资助(桂科回0639025)

摘　　要：目的:探讨先天性心脏病(以下简称先心病)患儿血清中的基质金属蛋白酶-2(MMP-2)、金属蛋白酶组织抑制物-1(TIMP-1)及血管内皮生长因子(VEGF)在小儿先天性心脏病不同肺动脉压力情况下的变化,予以前列腺素E1(PGE1)治疗和手术对上述因子表达的影响。方法:将81例左向右分流型先天性心脏病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<4.00 kPa)、轻度PH组21例(4.00 kPa≤SPAP<5.33 kPa)、中度PH组21例(5.33 kPa≤SPAP<9.33 kPa)、重度PH组23例(SPAP≥9.33 kPa),以21例正常体检儿为对照组;19例接受前列腺素E1(PGE1)治疗;24例接受手术治疗。用ELISA法检测血清MMP-2、TIMP-1和VEGF的含量,并计算MMP-2/TIMP-1的比值。结果:与正常组比较,先心病各组MMP-2、VEGF均显著增高(各组MMP-2均P<0.01;VEGF在非、轻、重度PH3组均P<0.05,中度PH组P<0.01);TIMP-1的含量均显著增高(轻、中度PH组P<0.05,重度PH组P<0.01);非PH、轻度PH及中度PH组MMP-2/TIMP-1的比值均显著增高(均P<0.05)。经PGE1药物治疗14 d后,MMP-2、TIMP-1和VEGF的含量与治疗前比较均显著下降(均P<0.01)。手术治疗7 d后,MMP-2、TIMP-1的含量、MMP-2/TIMP-1比值与VEGF的含量均呈显著下降(MMP-2、TIMP-1、VEGF均P<0.01,MMP-2/TIMP-1,P<0.05)。结论:①左向右分流型先心病血清MMP-2、VEGF显著升高,这可能与先心病肺动脉高压形成及肺血管重构有关。②PGE1可有效地降低先心病并发PH患儿血清MMP-2、TIMP-1和VEGF的表达。③在手术后1周,先心病并发轻、中度PH患儿血清MMP-2、TIMP-1、MMP-2/TIMP-1和VEGF的表达显著降低。AIM： To investigate the roles of serum matrix metalloproteinase-2 （MMP-2）, metalloproteinase inhibition-1 （TIMP-1） and vascular endothelial growth factor （VEGF） in pulmonary vascular reconstitution in patients with congenital heart disease. METHODS： According to the preoperative pulmonary arterial systolic pressure （SPAP）, 81 patients with congenital heart disease of left-to-right shunt type were divided into four groups： no pulmonary hypertension （PH） group （n = 16, SPAP 〈 4. 00 kPa）, mild PH group （n =21, 4.00 kPa≤SPAP 〈5.33 kPa）, medium PH group （n =21, 5.33 kPa≤SPAP 〈9. 33 kPa） and severe PH （n = 23, SPAP≥9. 33 kPa）. Twenty one healthy children undergoing routine physical examination were included as the control group. Of the 84 patients, 19 were comprehensively treated with PGE1 and 24 were treated surgically. Concentrations of serum MMP-2, TIMP-1 and VEGF were measured with ELISA and the ratio of MMP-2/TIMP-1 was calculated. RESULTS： Compared with those of the control group, concentrations of serum MMP-2 and VEGF obviously increased in all four groups and the levels of TIMP-1 significantly increased in mild, medium and severe groups. The ratio of MMP-2/TIMP-1 also significantly increased in no PH, mild PH and medium PH groups. After treatment with PGE1 for 14 days, the levels of serum MMP-2, TIMP-1 and VEGF all obviously decreased. Surgical intervention also signifi- cantly decreased the levels of MMP-2, TIMP-1, MMP-2/TIMP-1 and VEGF. CONCLUSION： Serum VEGF and MMP-2 may synergistically contribute to pulmonary vascular reeonstitution in patients with congenital heart disease of left-to-right shunt type. PGE1 significantly decreases the levels of serum MMP-2, TIMP-1 and VEGF, which may show how PGE1 is involved in reversing pulmonary vascular remodeling. Levels of serum VEGF, MMP-2, MMP-2/TIMP-1 and TIMP-1 decrease significantly 7 days postoperatively.

关 键 词：先天性心脏病 肺动脉高压 基质金属蛋白酶 内皮生长因子 金属蛋白酶组织抑制物-1 

分 类 号：R725.4[医药卫生—儿科]