瘦素调控血管新生机理的研究
发布时间：2019-03-15 21:29
【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Cocl_2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
[Abstract]:Aim: to study the effects of leptin (Leptin) on proliferation, migration and tubular structure formation of umbilical vein endothelial cells (HUVECs). We further studied whether the angiogenesis-promoting effect of Leptin was related to the up-regulation of HIF-1 伪, and then to promote the expression of downstream target gene VEGF, and whether it was mediated by PI3K and ERK1/2 signal transduction pathway. Methods: HUVECs. was isolated, cultured and identified. The effects of Leptin on proliferation, migration and angiogenesis of HUVECs in vitro were detected. Semi-quantitative RT-PCR was used to detect the expression of HIF-1 伪 and VEGFmRNA. Western blot was used to detect the expression of HIF-1 伪 and VEGF protein. Results: Leptin promoted the proliferation of HUVECs in a dose-dependent manner. When Leptin 100 ng/mL, the migration rate of HUVECs increased significantly, which was 2.2 times higher than that of the control group. This effect could be blocked by PI3K inhibitor Ly294002 and ERK1/2 inhibitor PD98059. Leptin up-regulated the expression of HUVECS HIF-1 伪 and VEGF protein in a dose-dependent manner, which depended on the up-regulation of Leptin-induced expression of HIF-1 伪 and VEGF mRNA in HUVECs. Cocl_2, a hypoxia simulator, also promoted the expression of HUVECs HIF-1 伪 protein, but had no effect on the expression of HIF-1 伪 mRNA. PI3K inhibitor Ly294002 (20 渭 mol / L) or ERK1/2 inhibitor PD98059 (20 渭 mol / L) could inhibit the up-regulation of HIF-1 伪 and VEGF protein expression induced by Leptin, but had no effect on the expression of HIF-1 伪 and VEGF mRNA. Conclusion: Leptin promotes angiogenesis by promoting HUVECs proliferation, migration and angiogenesis in vitro. Leptin can promote angiogenesis by up-regulating the expression of HIF-1 伪 at transcription and translation levels. To promote the expression of VEGF. PP3K and ERK1/2 signaling pathway
【学位授予单位】：中国协和医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R33
本文编号：2441003
[Abstract]:Aim: to study the effects of leptin (Leptin) on proliferation, migration and tubular structure formation of umbilical vein endothelial cells (HUVECs). We further studied whether the angiogenesis-promoting effect of Leptin was related to the up-regulation of HIF-1 伪, and then to promote the expression of downstream target gene VEGF, and whether it was mediated by PI3K and ERK1/2 signal transduction pathway. Methods: HUVECs. was isolated, cultured and identified. The effects of Leptin on proliferation, migration and angiogenesis of HUVECs in vitro were detected. Semi-quantitative RT-PCR was used to detect the expression of HIF-1 伪 and VEGFmRNA. Western blot was used to detect the expression of HIF-1 伪 and VEGF protein. Results: Leptin promoted the proliferation of HUVECs in a dose-dependent manner. When Leptin 100 ng/mL, the migration rate of HUVECs increased significantly, which was 2.2 times higher than that of the control group. This effect could be blocked by PI3K inhibitor Ly294002 and ERK1/2 inhibitor PD98059. Leptin up-regulated the expression of HUVECS HIF-1 伪 and VEGF protein in a dose-dependent manner, which depended on the up-regulation of Leptin-induced expression of HIF-1 伪 and VEGF mRNA in HUVECs. Cocl_2, a hypoxia simulator, also promoted the expression of HUVECs HIF-1 伪 protein, but had no effect on the expression of HIF-1 伪 mRNA. PI3K inhibitor Ly294002 (20 渭 mol / L) or ERK1/2 inhibitor PD98059 (20 渭 mol / L) could inhibit the up-regulation of HIF-1 伪 and VEGF protein expression induced by Leptin, but had no effect on the expression of HIF-1 伪 and VEGF mRNA. Conclusion: Leptin promotes angiogenesis by promoting HUVECs proliferation, migration and angiogenesis in vitro. Leptin can promote angiogenesis by up-regulating the expression of HIF-1 伪 at transcription and translation levels. To promote the expression of VEGF. PP3K and ERK1/2 signaling pathway
【学位授予单位】：中国协和医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R33
【引证文献】
相关期刊论文 前1条
1 王春艳;杜瑞平;张兴夫;高民;;瘦素及其生理功能概述[J];动物营养学报;2012年03期
本文编号：2441003
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