依那普利对高肺血流量大鼠血浆NO和肺血管内皮生长因子表达的影响

Effect of enalapril on serum nitric oxide and expression of vascular endothelial growth factor in high pulmonary blood flow rats

目的观察血管紧张素转换酶抑制剂(ACEI)对高肺血流大鼠血浆NO含量、肺组织中血管内皮生长因子(VEGF)表达的影响。方法23只雄性SD大鼠随机分为对照组(n=7)、分流组(n=8)和分流+依那普利组(n=8)。对分流组和分流+依那普利组大鼠行腹主动脉-下腔静脉分流术,并以依那普利进行干预。11周后测定mPAP、RV/BW和RV/LV+S比值,观测肺血管显微结构的变化,计算WT%及WA%。测定血浆NO含量,肺组织中VEGF的表达。结果(1)分流组大鼠mPAP、RV/BW及RV/LV+S比值明显高于对照组。肺中、小型肌型动脉WT%和WA%明显升高。血浆NO含量较对照组有下降趋势,肺动脉内皮细胞和平滑肌细胞VEGF表答明显增强。(2)分流+依那普利组大鼠mPAP、RV/BW、RV/LV+S比值明显低于分流组,中、小型肺肌型动脉WT%和WA%明显降低,血浆NO含量较分流组有明显增加,肺动脉内皮细胞VEGF表达减少。结论ACEI能减缓高肺血流量所致肺动脉高压和肺血管重塑,NO、VEGF可能在其中起重要作用。

To explore the effect of ACEI on pulmonary hypertension and pulmonary vascular structural remodeling induced by high pulmonary flood flow in rats. Methods Twenty-three male SD rats were randomly divided into control group （C）, shunting group（S）, and shunting with enalapril group（SE）. Abdominal aorta and inferior vena cava shunting were produced in groups S and SE. After ll-week shunting, mPAP of each rat was measured. RV/BW and RV/LV＋S were documented. Pulmonary vascular microstructure was measured. WT% and WA% were calculated. Meanwhile,the concentration of plasma NO was measured. The expressions of VEGF by pulmonary arteries were semiquantitative. Results After 11-week aortocaval shunting, mPAP RV/BW and RV/ LV＋S were significantly increased in group S compared with those in group C. Muscularization of small pulmonary artery, WT% and WA% of pulmonary muscularized arteries were obviously increased in group S compared with those in group C. Meanwhile, plasma NO concentration was significantly decreased, VEGF protein expressions significantly increased in endothelial and smooth muscle cells of the pulmonary artery in group S than that in group C. However, mPAP, RV/BW and RV/LV＋S were significantly decreased in group SE compared with those in group S. WT% and WA% of pulmonary muscularized arteries were obviously decreased in group SE compared with those in group S. Meanwhile, plasma NO concentration was significantly increased, VEGF protein expression reduced in endothelial cells of the pulmonary artery in group SE than that in group S. Conclusion Enalapril might ameliorate pulmonary hypertension and pulmonary vascular structure remodeling induced by high pulmonary blood flow. NO and VEGF might play important roles in the pathogenesis of it.