缺氧性肺动脉高压新生大鼠肺血管重塑的研究

Pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension

目的通过建立新生大鼠缺氧性肺动脉高压(hypoxia-induced pulmonary hypertension,HPH)模型,探讨HPH新生大鼠发病过程中肺血管重塑的变化。方法将96只新生Wistar大鼠随机分为2组:缺氧组和常氧对照组,缺氧组建立新生大鼠HPH模型。分别于缺氧3、5、7、10、14、21 d取缺氧组及对照组同日龄新生大鼠各8只测定其平均肺动脉压(mean pulmonary arteria pressure,mPAP)、右心室肥大指数(right ventricle hypertrophy in-dex,RVHI),血管重塑指标MT%、MA%,观察肺血管超微结构。结果缺氧组大鼠在缺氧3、5、7、10、14、21 dmPAP持续上升,明显高于对照组(P<0.05);随着缺氧时间的延长,差异更为显著。缺氧7 d后MT%、MA%、RVHI明显高于对照组(P<0.05);随着缺氧时间的延长,差异同样更为显著。透射电镜显示,缺氧7 d后大鼠肺小动脉内膜增厚,内皮细胞增生、变性,细胞器增多;细胞外基质见胶原纤维沉积;出现肺血管重塑改变。结论新生大鼠缺氧3～5 d肺动脉压力增高,处于肺血管痉挛阶段;缺氧7 d后肺血管出现重塑,右心室肥厚,出现不可逆变化;随着缺氧时间延长,上述变化加剧。

Objective To study the changes of pulmonary vascular remodeling in the pathogenesis of hypoxia-induced pulmonary hypertension（HPH） in neonatal rats. Methods Ninety-six newborn Wistar rats were randomly divided into an HPH group（hypoxia exposure） and a control group（room air exposure）.The mean pulmonary arteria pressure（mPAP）,right ventricle hypertrophy index（RVHI）,and vascular remodeling indexes MT% and MA% were measured 3,5,7,10,14 and 21 days after exposure（n=8 each time point）.The ultrastructure of pulmonary vascular was observed under a transmission electron microscope. Results mPAP in the HPH group 3,5,7,10,14 and 21 days after hypoxia exposure increased compared with the control group（P0.05）.With the prolonged hypoxia time,mPAP in the HPH group increased more significantly.MT%,MA% and RVHI increased significantly in the HPH group after 7 days of hypoxia exposure in a time-dependent manner compared with the control group（P0.05）.The transmission electron microscopy demonstrated that small pulmonary arterials became thickened,endothelial cell hyperplasia and degeneration,and organelles increased in the HPH group after 7 days of hypoxia exposure.Besides,collagen deposition in the extracellular matrix and the changes of pulmonary vascular remodeling were observed. Conclusions mPAP increases between 3 and 5 days of hypoxia exposure,resulting from pulmonary vascular spasm caused by hypoxia.After hypoxia of 7 days,the mPAP increases more significantly,pulmonary vascular remodeling occurs,and right ventricle becomes irreversibly hypertrophic.These changes may be intensified as the prolonged hypoxia time.