论文摘要
目的：研究瘦素（Leptin）对脐静脉内皮细胞（HUVECs）增殖、迁移和管状结构形成能力的影响。并进一步研究Leptin的促血管新生作用是否与之上调HIF-1α，进而促进下游靶基因VEGF表达有关及是否由PI3K and ERK1／2信号转导通路所介导。 方法：分离、培养和鉴定HUVECs。检测Leptin对HUVECs增殖、迁移和体外血管形成能力的影响。半定量RT-PCR检测HIF-1α、VEGFmRNA的表达。Western blot检测HIF-1α和VEGF蛋白的表达。 结果：Leptin能以剂量依赖性的方式促进HUVECs增殖。Leptin100ng／mL时，HUVECs的迁移率明显增加，是对照组的2.2倍，此作用能被PI3K抑制剂Ly294002和ERK1／2抑制剂PD98059所阻断。Leptin作用后，HUVECs体外形成血管能力增强。Leptin呈剂量依赖性的上调HUVECS HIF-1α和VEGF蛋白表达，此作用依赖于Leptin诱导的HIF-1α和VEGF mRNA表达上调。缺氧模拟剂Cocl2也能促进HUVECs HIF-1α蛋白表达，但对HIF-1αmRNA表达无影响，机制与Leptin不同。PI3K抑制剂Ly294002（20μmol／L）或ERK1／2抑制剂PD98059（20μmol／L）能够抑制Leptin诱导的HIF-1α和VEGF蛋白表达上调，但对HIF-1α和VEGF mRNA表达无影响。 结论：Leptin通过促进HUVECs增殖、迁移和体外血管形成等作用促进血管新生。Leptin的促血管新生作用与之能够在转录和翻译水平上调HIF-1α表达，进而促进VEGF表达有关。PP3K和ERK1／2信号途径
论文目录
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