VEGF在白藜芦醇缓解内皮细胞高通透性的作用

【作者】 田翀； 彭晓琳； 张嫦慧； 唐玉涵； 任玮叶； 孙秀发； 郝丽萍； 应晨江；

【机构】 华中科技大学同济医学院公共卫生学院营养与食品卫生学系；

【摘要】 目的:血管内皮细胞通透性的升高是内皮功能紊乱的主要表现之一,也是糖尿病并发心血管疾病的重要原因。但迄今对大血管内皮细胞通透性的研究甚少,本文拟研究白藜芦醇对内皮通透性的影响及机制。方法:在带滤膜的24孔培养板上,检测内皮细胞透性,Real time PCR测定VEGF和VEGFR2(VEGF受体2)mRNA,酶联免疫法和Western Blot分别检测VEGF蛋白分泌和VEGFR2蛋白表达水平。结果:白藜芦醇显著降低高糖引起的内皮通透性增高,且有剂量效应,rhVEGF也能显著升高内皮细胞通透性;高糖刺激显著升高培养细胞VEGF mRNA和蛋白水平,而白藜芦醇能降低高糖引起的VEGF和VEGFR2 mRNA和蛋白表达升高并降低内皮通透性。结论:白藜芦醇通过VEGF途径缓解高糖引起的内皮通透性升高。更多还原

【Abstract】 AIM:Recent studies implicate hyperglycemia as an important cause of macrovascular and microvascular complications in diabetes mellitus.However,the effects on permeability have been less described for macrovascular endothelial monolayer.In this study,the authors examined the effects of resveratrol(RSV),a phytochemical found in red wine,on endothelial permeability. Methods:BAECs(Bovine aortic endothelial cells) were incubated with or without resveratrol, recombined human VEGF(vascular endothelial growth factor) in the presence of high glucose (33mmol/l) or not.BAECs were seeded in the upper chamber of 0.4μm polycarbonate Transwell filters of a 24-well filtration microplate.After confluence was reached,permeability of macromolecules was measured by amount of FITC labeled dextran that got through the endothelial monolayer.The mRNA level of VEGF and KDR were measured by quantitative real time PCR.The expression of VEGF in the culture fluid and VEGFR2 in BAECs was determined using enzyme-linked immunosorbent assay and Western Blot separately. RESULTS:Compared with the control group,permeable fluorescence intensity was obviously increased in high glucose group,and RSV reversed the permeability increase caused by high glucose dose dependently,rhVEGF could induce great increase in permeability of macromolecules under normal condition,The Increase of mRNA and protein expression of VEGF and VEGFR2 caused by high glucose were reduced by RSV. CONCLUSION:High glucose induced hyperpermeability of macromolecules through endothelium is at least in part through the increase of VEGF and the effect is generated through VEGFR2.Resveratrol ameliorate the hyperglycemia-induced hyperpermeability in certain concentrations by regulating both the expression and secretion of VEGF and VEGFR2.更多还原