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目的采用球囊扩张人工房间隔造口+肺动脉环缩术建立肺血减少型先天性心脏病幼猪动物模型,探讨肺血流减少时未成熟肺血管形态学变化的病理生理机制。方法将出生1~2个月的幼猪20头按随机数字表法分为3组,对照组(C组,n=6):右胸小切口制成一过性肺血减少;轻度至中度肺动脉狭窄组(T1组,n=7),经右心房表面送入球囊扩张器行人工房间隔造口+肺动脉Banding环缩术,术中控制收缩期肺动脉环缩处压差(Trans-PABP)为20~30 mm Hg;重度肺动脉狭窄组(T2组,n=7):术中Trans-PABP≥30~50 mm Hg。3组于术后2个月取右肺中叶外侧段、大小为1.0 cm×0.8 cm×0.8 cm的肺组织,光学显微镜下观察远端肺细小动脉形态学改变,并采用双抗体夹心酶联免疫吸附法(ELISA)检测肺组织中血管内皮细胞生长因子(VEGF)和基质金属蛋白酶2(MMP-2)的含量。结果 T1组、T2组生存动物房间隔造口+肺动脉环缩术均获成功。术后2个月,T1组肺细小动脉内径明显大于C组(82.89±10.72μm vs.74.12±9.28μm;t=-5.892,P<0.05),T2组肺细小动脉内径明显大于C组(85.47±5.25μm vs.74.12±9.28μm;t=-6.325,P<0.05);T1组单位面积肺细小动脉数量(NAPSC)少于C组(229.70±88.00个/cm2vs.431.50±40.60个/cm2;t=39.526,P<0.05),T2组NAPSC少于C组(210.00±40.30个/cm2vs.431.50±40.60个/cm2;t=67.858,P<0.05);术后2个月,T1组肺组织MMP-2(58.30±19.60 ng/ml vs.81.20±16.70 ng/ml,t=14.261,P<0.05)和VEGF(17.80±3.00 pg/ml vs.21.40±3.80 pg/ml,t=8.482,P<0.05)表达较C组明显降低;T2组肺组织MMP-2(42.10±15.20 ng/ml vs.81.20±16.70 ng/ml,t=27.318,P<0.05)和VEGF(12.30±3.20 pg/ml vs.21.40±3.80 pg/ml,t=15.139,P<0.05)表达较C组明显降低。结论肺血减少型先天性心脏病幼猪肺组织细胞外基质发生构型重建,肺细小血管发育不良或退化。肺血减少时引起细胞外基质中结构性蛋白和细胞因子等成分变化是基质重塑的基础。
Objective To establish an animal model of pulmonary hypofractionation congenital heart disease by balloon dilatation of artificial atrial septostomy and pulmonary artery systole to explore the pathophysiological mechanism of immature pulmonary vascular morphology when pulmonary blood flow is reduced. Methods Twenty newborn piglets aged 1 ~ 2 months were divided into 3 groups according to random number table. The control group (C group, n = 6) Moderate pulmonary stenosis group (T1 group, n = 7), the right atrium through the balloon dilator into the artificial space septostomy + pulmonary artery Banding ring reduction, intraoperative systolic pulmonary artery systolic pressure drop (Trans- PABP) was 20-30 mm Hg. Severe pulmonary stenosis group (T2 group, n = 7): intraoperative Trans-PABP≥30-50 mm Hg. The lungs of the middle part of the right middle lobe, 1.0 cm × 0.8 cm × 0.8 cm in size, were harvested at 3 months after operation. Morphological changes of the distal small pulmonary arteries were observed under a light microscope and were detected by enzyme-linked immunosorbent assay The content of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP-2) in lung tissue were detected by ELISA. Results In T1 and T2 groups, the atrial septostomy and pulmonary systole were both successful. At 2 months after operation, the diameter of pulmonary arterioles in T1 group was significantly larger than that in C group (82.89 ± 10.72μm vs.74.12 ± 9.28μm; t = -5.892, P <0.05) ± 5.25μm vs.74.12 ± 9.28μm; t = -6.325, P <0.05). The number of pulmonary arterioles per unit area (NAPSC) in T1 group was less than that in C group (229.70 ± 88.00 / cm2 vs.431.50 ± 40.60 / cm2; t = 39.526, P <0.05). The NAPSC of T2 group was less than that of C group (210.00 ± 40.30 /cm2vs.431.50 ± 40.60ce / cm2; t = 67.858, P <0.05) (58.30 ± 19.60 ng / ml vs. 0.81 ± 16.70 ng / ml, t = 14.261, P <0.05) and VEGF (17.80 ± 3.00 pg / ml vs 2.1.40 ± 3.80 pg / ml, t = 8.482, P (P <0.05). The expression of MMP-2 in the lung tissue in the T2 group was significantly lower than that in the C group (42.10 ± 15.20 ng / ml vs.81.20 ± 16.70 ng / ml, t = 27.318, vs 2.1.40 ± 3.80 pg / ml, t = 15.139, P <0.05). Conclusion Reconstruction of extracellular matrix in lung tissue of young pig with congenital heart disease complicated with congenital heart disease with congenital heart disease, poor development or degeneration of pulmonary fine blood vessels. Changes in the composition of the structural proteins and cytokines in the extracellular matrix caused by the reduction of pulmonary blood flow are the basis for matrix remodeling.