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目的:探讨气管内转染血管内皮生长因子A(vascular endothelial growth factor-A，VEGF-A)在缺氧性肺动脉高压(hypoxia pulmonary hypertension，HPH)新生大鼠肺内的表达变化及其对肺动脉压力的影响。方法:选取新生大鼠72只，随机分为VEGF-A＋HPH组(气管内转染携带VEGF-A的腺病毒载体)、HPH组(气管内转染不携带VEGF-A的腺病毒载体)和对照组(气管内注入生理盐水)，每组24只，转染后VEGF-A＋HPH组和HPH组给予缺氧干预，对照组常氧条件下饲养。比较各组缺氧3 d时肺组织中标记腺病毒载体的增强型绿色荧光蛋白(enhanced green fluorescent protein，EGFP)荧光强度及VEGF-A＋HPH组缺氧3 d时肺、肝、脾、肾组织EGFP荧光强度；通过间接双重免疫荧光组织化学技术检测VEGF-A＋HPH组转染的VEGF-A与CD31标记的肺血管内皮细胞的关系；比较各组缺氧3 d、7 d、14 d时平均肺动脉压力及肺组织VEGF-A表达水平。结果:缺氧3 d时，VEGF-A＋HPH组肺组织的EGFP荧光强度明显高于肝、脾和肾脏组织以及对照组肺组织(n P<0.05)。VEGF-A＋HPH组转染的VEGF-A在CD31标记的肺血管内皮细胞处表达。缺氧3 d、7 d和14 d时，HPH组平均肺动脉压力高于对照组和VEGF-A＋HPH组(n P0.05)。缺氧3 d、7 d和14 d时，VEGF-A＋HPH组和HPH组肺组织内VEGF-A表达明显高于对照组(n P<0.05)；缺氧3 d、7 d时，VEGF-A＋HPH组肺组织中VEGF-A的表达明显高于HPH组(n P0.05)。n 结论:气管内靶向转染提高了HPH新生大鼠肺组织中VEGF-A的表达水平，进而降低了肺动脉压力。“,”Objective:To study the expression changes of vascular endothelial growth factor-A (VEGF-A) in the lungs of newborn rats with hypoxia pulmonary hypertension (HPH) using endotracheal transfection and its effects on pulmonary arterial pressure (PAP).Method:Seventy-two newborn Wistar rats were randomly assigned into the VEGF-A+ HPH group (endotracheal transfection with adenoviral vector carrying VEGF-A), the HPH group (endotracheal transfection with adenoviral vector not carrying VEGF-A) and the control group (endotracheal injection of normal saline). 24 newborn rats in each group. After transfection, the neonatal rats in the VEGF-A+ HPH group and the HPH group received 10%±0.5% oxygen, and the rats in the control group were fed under normoxic conditions. Hypoxia for 3 d, the fluorescence intensity of enhanced green fluorescent protein (EGFP) label of adenoviral vectors in the lung tissues of the three groups and the fluorescence intensity of EGFP within the lung tissue and liver, spleen, and kidney tissues of the VEGF-A+ HPH group were analyzed. The relationship between VEGF-A and the pulmonary vascular endothelial cells labeled by platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) was detected using indirect double immunofluorescence histochemistry. After hypoxia for 3 d, 7 d and 14 d, PAP were analyzed and the protein levels of VEGF-A in the lung tissues of each group were examined using immunohistochemistry method.Result:After hypoxia for 3 d, the fluorescence intensity of lung tissue in the VEGF-A+ HPH group was higher than the liver, spleen and kidney tissues and higher than lung tissues in the control group (n P<0.05). VEGF-A was expressed at CD31-labeled pulmonary vascular endothelial cells. The PAP of the HPH group was higher than the control group and the VEGF-A+ HPH group (n P0.05). At 3 d, 7 d and 14 d after hypoxia, the protein expression of VEGF-A in the lung tissues of the VEGF-A+ HPH group and the HPH group was higher than the control group (n P<0.05). At 3 d and 7 d after hypoxia, the expression of VEGF-A in the lung tissues of the VEGF-A+ HPH group was higher than the HPH group (n P0.05).n Conclusion:Targeted endotracheal transfection increased the expression of VEGF-A in the lung tissue of neonatal rats with HPH and decreased PAP. This may play a protective role in the pathogenesis of the disease, providing new approach for the prevention and treatment of neonatal HPH.