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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。
Objective: To investigate the changes of serum MMP-2, TIMP-1 and VEGF in children with congenital heart disease (CHD) Infantile congenital heart disease under different pulmonary arterial pressure changes in patients with prostaglandin E1 (PGE1) treatment and surgery on the expression of these factors. Methods: 81 cases of left-right shunt congenital heart disease were divided into 4 groups according to the pre-treatment pulmonary arterial systolic pressure (SPAP): 16 cases (SPAP <4.00 kPa) in non-pulmonary hypertension group, 21 cases in mild PH group (4.00 kPa ≤ SPAP <5.33 kPa), moderate PH group (21 cases, 5.33 kPa ≤ SPAP <9.33 kPa), 23 cases of severe PH group (SPAP ≥ 9.33 kPa) Received prostaglandin E1 (PGE1) treatment; 24 patients underwent surgical treatment. Serum levels of MMP-2, TIMP-1 and VEGF were measured by ELISA, and the ratio of MMP-2 / TIMP-1 was calculated. Results: The levels of MMP-2 and VEGF in each group were significantly higher than those in the normal group (P <0.01 for all the groups), VEGF (P <0.05 for non-mild and severe PH3 groups, P < 0.01). The levels of TIMP-1 were significantly increased (P <0.05 in mild and moderate PH group and P <0.01 in severe PH group). The ratio of MMP-2 / TIMP-1 in non PH group, mild PH group and moderate PH group Were significantly higher (all P <0.05). After 14 days of PGE1 treatment, the levels of MMP-2, TIMP-1 and VEGF were significantly decreased (all P <0.01). The content of MMP-2, TIMP-1, the ratio of MMP-2 / TIMP-1 and the content of VEGF were significantly decreased after 7 days of operation (MMP-2, TIMP-1, VEGF, P <0.01, MMP- /TIMP-1,P<0.05). Conclusion: ① The serum levels of MMP-2 and VEGF are significantly increased in left-to-right shunt congenital heart disease, which may be related to the formation of pulmonary hypertension and pulmonary vascular remodeling. ② PGE1 can effectively reduce the serum levels of MMP-2, TIMP-1 and VEGF in children with congenital heart disease complicated with PH. ③ At 1 week after surgery, the expression of MMP-2, TIMP-1, MMP-2 / TIMP-1 and VEGF were significantly decreased in CHD patients with mild to moderate PH.