HIF和VEGF在低氧性肺动脉高压中的调控作用

The effects of HIF and VEGF on pulmonary hypertension induced by chronic hypoxic hypercapnia

目的:观察低氧诱导因子-1 α(HIF-1α)蛋白和血管内皮生长因子(VEGF)蛋白在低氧性肺动脉高压小鼠肺内的表达,探讨HIF和VEGF在其中的调控作用。方法:建立低氧性肺动脉高压小鼠模型,SPF级雄性C57BL/6小鼠16只,随机分为正常对照组(C组),低氧、高二氧化碳4w组(H组),每组8只。测二组小鼠的右心室收缩压(RVSP)和右心室重量比RV/(LV+S)。光镜下观察右心室和肺组织病理学改变。应用免疫组化技术检测肺细小动脉上HIF-1 α蛋白和VEGF蛋白的表达。结果:H组小鼠RVSP明显高于C组,且RV/(LV+S)亦有增加。光镜下肺细小动脉管腔变窄管壁增厚,中膜平滑肌细胞肥大增生。免疫组织化学显示:H组小鼠肺细小动脉HIF-1 α蛋白和VEGF蛋白免疫组化吸光度高于对照组;VEGF蛋白与HIF-1 α蛋白表达呈正相关。结论:慢性低氧使HIF-1 α蛋白和VEGF蛋白在肺细小动脉表达增加,二者参与小鼠肺动脉高压的形成和发展过程。

Objective：To explore the expression of Hypoxia-inducible factor 1α（HIF-1α）pro-tein and vascular endothelial growth factor（VEGF） protein in mice with pulmonary hypertension induced by chronic hypoxic hypercapnia, and investigate whether HIF signal path to regulate the expression of VEGF. Methods： Sixteen male C57bl/6 mice were randomly divided into two groups： the control group （group C） and the group with hypoxic hypercapnia for 4 weeks （group H）. The right ventricular systolic pressure （RVSP） and the ratio of RV/（LV＋S）） were measured. Lung sections were stained with hematoxylin and eosin （H＆E） for morphologic studies under light microscope. The expression of HIF-1αprotein and VEGF protein of pulmonary arterioles was also observed with immunohistochemistry. Results： ①The values of the RVSP, RV/LV＋S in group H were significantly higher than that in group C. ②The vessel walls of the pulmonary arterioles of group H were thicken, the smooth muscle cells in tunica media were proliferated and the lumens of the pulmonary arterioles were narrowed under light microscope. ③Both HIF-1αprotein and VEGF protein staining were positive in the lung of pulmonary arterioles of group H with immunohistochemistry. The average optical density of HIF-1αand VEGF protein with immunohistochemistry in the pulmonary arterioles in group H was significantly higher than that in group C. There was positive correlation between VEGF protein and HIF-1α protein. Conclusion： HIF-1αprotein and VEGF protein are induced to express by chronic hypoxic, and involved in the pathogenesis with pulmonary hypertension in mice.