Effect of dexamethasone on expression of hypoxia inducible factor-1α and vascular endothelial growth factor in hypoxic mice

Abstract

业已发现缺氧与肿瘤发生、发展关系密切。本研究的目的是观察地塞米松对低氧小鼠肺组织中缺氧诱导因子1α(hypoxiainduciblefactor1α,HIF1α)及血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)表达的影响,探讨缺氧与血管新生的关系及地塞米松的作用机制。方法 实验用雄性昆明小鼠,随机分为对照组和三个实验组(缺氧3天组、缺氧6天组、缺氧+激素组)。用免疫组织化学技术检测小鼠肺组织中HIF1α和VEGF蛋白的表达。结果 缺氧组小鼠HIF1α和VEGF蛋白表达均较对照组显著增加(P < 0.05);缺氧+激素组与缺氧组比较,HIF1α和VEGF蛋白表达显著下降(P < 0.05)。HIF1α与VEGF表达呈正相关(r=0.730,P=0.007)。结论 缺氧可以上调小鼠肺组织中VEGF和HIF1α的表达,而地塞米松可抑制低氧小鼠VEGF和HIF1α的表达,具有抗血管生成的作用。

Background and objective It has been proved that hypoxia is closely related to oncogenesis and development of tumor. The aim of this study is to observe the effect of dexamethasone on expression of hypoxia inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in lung tissues of hypoxic mice, and to investigate the relationship between hypoxia and angiogenesis and mechanism of dexamethasone. Methods The Kunming mice were randomly divided into control group and three experimental groups (3-day hypoxia group, 6-day hypoxia group, and hypoxia+dexamethasone group). HIF-1α and VEGF protein expression was detected in lung tissues of mice by immunohistochemistry. Results Expression of HIF-1α and VEGF significantly increased in hypoxia group compared with control group (P < 0.05). Compared with hypoxia group, expression of HIF-1α and VEGF decreased dramatically in hypoxia+dexamethasone group (P < 0.05). A positive correlation was found between the expression of HIF-1α and VEGF (r=0.730, P=0.007). Conclusion Hypoxia can increase the expression of VEGF and HIF-1α in lung tissues of mice. Dexamethasone can inhibit the expression of VEGF and HIF-1α of hypoxic mice and it may have anti-angiogenetic effect.