大鼠左全肺切除促进肺血管重塑

Pulmonary vascular remodeling after left lung pneumonectomy in rats

目的探讨大鼠左全肺切除后是否导致肺血管重塑,以及低氧诱导因子-1α(HIF-1α)和血管内皮细胞生长因子(VEGF)在肺血管重塑中的作用。方法切除大鼠左全肺建立动物模型,12周后检测平均肺动脉压(m PAP)和动脉血氧分压(Pa O2),在电镜、光镜下观察大鼠肺小血管结构改变,计算其肌型动脉(MA)、部分肌型动脉(PMA)、非肌型动脉(NMA)、中膜厚度(MTV)、中膜面积(MAV)及其百分比作为肺血管重塑指标。通过免疫组组化学法检测HIF-1α和VEGF在肺动脉管壁的表达。结果实验组m PAP、MA%、PMA%、MTV、MAV、MTV%和MAV%明显高于对照组(P﹤0.01),Pa O2、NMA%明显低于对照组(P<0.01)。实验组肺动脉壁HIF-1α及VEGF的IOD值(26.47±4.16,42.04±3.79)明显高于对照组(6.12±2.14,11.53±2.29)(P<0.01)。相关分析表明,HIF-1α及VEGF的表达强度与Pa O2呈负相关,与MTV%及MAV%呈正相关,HIF-1α与VEGF的表达强度呈正相关。结论通过大鼠左全肺切除可以建立肺血管重塑动物模型。低氧血症是大鼠左全肺切除后肺血管重塑的重要因素,HIF-1α与VEGF在低氧导致的肺血管重塑过程中起着重要作用。

Objective To investigate the existence of pulmonary vascular remodeling after left pneumonectomy in rats and the role of hypoxia inducible factor-lα（ HIF-1α） and vascular endothelial growth factor（ VEGF） in pulmonary vascular remodeling. Methods Twenty-four healthy male Sprague-Dawley rats were randomly divided into experimental and control groups,12 in each group. The rat models of pulmonary vascular remodeling were created by open-chest left pneumonectomy. After 12 weeks of feeding,the mean pulmonary artery pressure（ m PAP） and partial pressure of arterial oxygen（ Pa O2） of each rat were measured. The ultrastructure of small arteries in the lung specimens were examined by electron microscopy. Muscularized degree of three kinds of small pulmonary vessels（ muscularized artery MA,partially muscularized artery PMA,and non-muscularized artery NMA） were observed by light microscopy,and the percentage of each kind of pulmonary arteries（ MA%,PMA%,NMA%） were calculated. Arterial external diameter,media thickness of vessel（ MTV）,total vascular area,media area of vessel（ MAV）,MTV% and MAV% were calculated as indicators of pulmonary vascular remodeling. The expressions of HIF-1α and VEGF in artery were detected by immunohistochemistry. Results The values of m PAP,MA%,PMA%,MTV,MAV,MTV% and MAV% in the experimental group were significantly higher than those in the control group（ P〈0. 01）,but the value of Pa O2 and NMA% were significantly lower than those in the control group（ P〈0. 01）. The IOD value of HIF-1α and VEGF expressed in the pulmonary arterial wall of theexperimental group were 26. 47 ± 4. 16 and 42. 04 ± 3. 79,respectively,significantly higher than those in the control group（ 6. 12 ± 2. 14 and 11. 53 ± 2. 29,P〈0. 01）. Linear correlation analysis showed that the expression of HIF-1α and VEGF was positively correlated with MTV% and MAV%,negatively correlated with PaO 2,and the HIF-1α expression was positively correlated with VEGF expression. Conclusions A rat model of pulmonary vascular remodeling can be successfully established by left pneumonectomy. Hypoxia is a key factor in the development of pulmonary vascular remodeling,HIF-1αand VEGF may play an important role in its pathogenesis.