缺氧对血管内皮生长因子诱导牛冠状动脉内皮细胞脂蛋白通透性升高的调控及丹酚酸B的抑制作用

Vascular endothelial growth factor-induced hyperpermeability in bovine coronary endothelial cell regulated by hypoxia and the inhibitory effect of salvianolic acid B

目的 为了了解缺氧对血管内皮生长因子(VEGF)增强血管内皮细胞通透性作用的影响及其与动脉粥样硬化的关系 ,考察了正常和缺氧状态下VEGF对体外培养牛冠状动脉内皮细胞 (BCEC)脂蛋白通透性的影响及丹酚酸B的抑制作用。方法 正常及缺氧条件下 ,将VEGF及丹酚酸B加入BCEC共孵育 ,用SN 695型液闪计数器测 [12 5I]低密度脂蛋白([12 5I]LDL)通过BCEC的百分率。结果 VEGF可显著增强BCEC对 [12 5I]LDL的通透性 ,这种增加具有浓度依赖性。缺氧 3h可促进VEGF所致的的通透性增加。丹酚酸B在正常和缺氧条件下均显著抑制VEGF诱导的BCEC通透性升高。结论 VEGF可增强血管内皮细胞的通透性 ,可能在动脉粥样硬化的形成和发展过程中起一定作用。

AIM In order to understand the regulation of hypoxia on the vascular endothelial growth factor(VEGF) permeability action on vascular endothelial cells, particularly in relation to the risk of development of atherosclerosis, the effect of recombinant human VEGF on the low density lipoprotein(LDL) permeability of bovine aortic endothelial cells(BCEC) was observed under the hypoxia condition as well as the protection of Chinese traditional medicine salvianolic acid B in vitro. METHODS Under normal or hypoxia condition, the confluence BCEC monolayers were cultured with normal medium and with medium containing VEGF or salvianolic acid B. The LDL flux across the monolayers was then performed, and the radioactivity was measured by SN-695 automatic liquid scintillation counter. RESULTS Addition of VEGF to the BCEC monolayers significantly increased the permeability of the monolayer to LDL (P<0.01). The permeability-increasing activity of VEGF on the BCEC monolayers was concentration dependent. Hypoxia 3 h on endothelial cells increased VEGF-induced hyperpermeability. Salvianolic acid B markedly inhibited the VEGF-induced hyperpermeability in BCECs (P<0.01) under both normal and hypoxia condition. CONCLUSION VEGF increases permeability on vascular endothelial cells, which may play a role in the formation and development of atherosclerosis. Salvianolic acid B has inhibitory effect on VEGF-induced hyperpermeability in BCEC.