内膜新生性肺血管重构肺动脉高压大鼠模型的建立及评价

背景：目前尚缺乏简单易行、实用、操作性强的血管内膜新生性肺血管重构肺动脉高压动物模型。目的：建立内膜新生性肺血管重构大鼠肺动脉高压模型。方法：40只雄性SD大鼠随机分为2组：M＋P组（n=26）大鼠行左肺切除,2周后皮下注射野百合碱60mg/kg;对照组（n=14）大鼠仅行假手术处理。于术后5周检测肺动脉压、右心室/（左心室＋室间隔）质量的比值,同时观察右肺动脉病理形态学改变。以光镜下每1mm2面积内Ⅷ因子标记阳性的直径小于100μm的肺血管数评价肺内微血管密度。结果与结论：M＋P组大鼠存活率85%（22/26）,对照组存活率为100%（14/14）。与对照组相比,M＋P组大鼠肺动脉压力和右心室/（左心室＋室间隔）质量的比值明显增高（P〈0.01）;与对照组相比,M＋P组大鼠肺内直径为50-100μm和100-150μm的肌型小动脉中膜相对厚度均显著增加（P〈0.01）,肺内微血管密度显著减少（P〈0.01）。光镜显示M＋P组大鼠注射野百合碱后5周肌型肺小动脉中膜明显增厚,肺腺泡内小动脉明显肌化、内膜增厚。对照组大鼠肺小动脉未见血管结构重建。实验成功建立了内膜新生性肺血管重构大鼠肺动脉高压模型,操作相时简便,动物死亡率较低。

Establishment of a neointimal model of pulmonary hypertension induced by monocrotaline injury plus pneumonectomy in rats

BACKGROUND：There is currently a lack of simple, practical, workable neointimal models of pulmonary hypertension in rats. OBJECTIVE：To establish a neointimal model of pulmonary hypertension by monocrtaline injury plus pneumonectomy in rats. METHODS：Forty male SD rats were randomly divided into two groups： monocrtaline＋pneumonectomy group （experimental group） was subjected to left pneumonectomy followed by monocrotaline injected 2 weeks later （n=26）; Control group only underwent sham operation （n=14）. Pulmonary artery pressure, ventricular weight, and pulmonary artery morphology were evaluated at 5 weeks after operation in each group. Factor VIII-positive capillaries that were less than 100 μm in diameter were counted under microscopy for 10 randomly selected fields per specimen. The capillary density was determined as the average number of factor VIII-positive capillaries per 1 mm2. RESULTS AND CONCLUSION：Four weeks after operation, 85% rats survived （22/26） in the experimental group, and 100% in the control group （14/14）. The experimental group had significantly higher mean pulmonary artery pressures and ratio of right ventricular and left ventricular plus septal weights, as well as percent wall thickness of muscular pulmonary arteries ranging from 50 to 100 μm diameter and from 100 to 150 μm diameter were significantly increased as compared with the control group （P 0.01）. Pulmonary capillary density was less in the experimental group than in the control group （P 0.01）. Historic examination showed significant medial hypertrophy of muscularized pulmonary arteries and muscularization of intra-acinar pulmonary arteries and intimal thickening developed in right lung intracinar pulmonary arteries in the experimental group. However, there was no evidence of pulmonary vascular remodeling in the control group. Hemodynamic pulmonary hypertension and neointimal lesions could be quickly induced at 5 weeks after pneumonectomy plus monocrotaline injury. This method was easily performed and mortality of rats was relatively low.