肺血减少型先天性心脏病幼猪动物模型的立及其未成熟肺血管的形态学变化

目的 采用一种新型的杂交方法建立肺血减少型先天性心脏病幼猪动物模型,探讨肺血减少对未成熟肺血管发育形态学的影响.方法 采用生后1～2个月的实验用小型幼猪,共20只.随机分为3组.假手术组(S组,n=6):右进胸微创小切口制成一过性肺血减少;手术组1(T1组,n=7):右进胸微创小切口,经右心房表面送入自制球囊扩张器行人工房间隔造口术,并且肺动脉Banding 环缩,使跨环缩处压差为20～30 mm Hg(1 mm Hg=0.133 kPa);手术组2(T2组,n=7):手术过程同T1组,使跨环缩处压差为30～ 50 mm Hg.三组均于开胸后、手术结束时、术后2个月取右肺中叶外侧段大小1.0 cm ×0.8 cm ×0.8 cm的肺组织,weihgt弹性纤维+van Gieson染色,光镜下观察其病理形态学变化.结果 S组动物存活5只,T1组动物存活6只,T2组动物存活5只,T1组、T2组在开胸后、手术结束时肺细小动脉内径与S组之间的差异均无统计学意义(P均＞0.05),T1组术后2个月时肺细小动脉内径明显高于S组(P＜0.05),T2组术后2个月时肺细小动脉内径明显高于S组(P＜0.01),T1组术后2个月时单位面积肺细小动脉数目(APSC)明显低于S组(P＜0.05),T2组术后2个月时肺APSC明显低于S组(P＜0.01),提示肺细小动脉中膜变薄、管腔扩张,同时伴有外周肺小动脉数量减少,并随肺血流的减少,细小动脉发育不良程度加重.结论 肺血减少时幼猪肺细小动脉发育呈现明显不良或退化,说明保持正常的肺血流或尽早改善肺血减少状态是促进外周肺血管正常发育和改善全身状况的关键.

Establishment of a cyanotic congenital heart defect porcine model with decreased pulmonary blood flow

Objective To establish a porcine model of congenital heart disease with decreased pulmonary blood to explore the morphological changes of immature pulmonary vascular vessels.Methods Twenty piglets (one to two-month-old ) were randomly divided into three groups:sham-operated group (group S,n =6),small incisions on the right chest,produced a transient reduction in pulmonary blood;Operation group 1 ( group T1,n =7),small incisions on the right chest,producing artificial atrial defect with self-made dilator and simultaneous banding pulmonary artery to generate a systolic pressure gradient between 20 - 30 mm Hg(1 m Hg =0.133 kPa) ; Operation group 2(group T2,n =7):operation procedure was similar as group T1 with systolic pressure gradient between 30 -50 mm Hg.Lung tissue from right middle lobe ( 1.0 cm × 0.8 cm × 0.8 cm) was taken immediately after thoracotomy,at the end of surgery and at 2 months after operation and stained by Weigert (elastic fiber) and van Gieson (collagen) methods to observe the morphological changes.Results Five animals survived in Group S,6 animals survived in group T1 and 5 animals survived in group T2.The inside diameter of pulmonary arterioles after thoracotomy and at the end of surgery was similar among the three groups (P ＞0.05).At 2 months after operation,the inside diameter of pulmonary artery was significantly higher in group T1 and T2 than in group S (all P ＜ 0.05 )while the number of pulmonary small artery per square centimeter (APSC) of group T1 and T2 was significantly lower than that of group S ( all P ＜ 0.05).Tunica media of pulmonary artery was thinner and vascular lumen was larger in group T1 and T2 compared to those of group S.Conclusion In this piglets model with reduced pulmonary blood,the pulmonary arterioles underwent dysplastic changes.Thus,pulmonary blood flow is an important determinant for the physiological development of pulmonary artery.