【作者】 于珮； 于德民； 齐建成； 王静； 张秋梅； 汤云昭； 邢秋玲；

【Author】 YU Pei;YU De-min;QI Jian-cheng;WANG Jing;ZHANG Qiu-mei;XING Qiu-ling;ZHANG Jing-yun;LI Ming-zhen;Department of Diabetic Nephropathy,Tianjin Medical University Metabolic Disease Hospital;

【机构】 天津医科大学代谢病医院；

【摘要】 目的:用人脐静脉内皮细胞观察高糖对内皮细胞增殖及对PI3K-Akt信号途径的影响。方法:用不同浓度的D-葡萄糖处理人脐静脉内皮细胞,观察其增殖情况及Akt,磷酸化Akt(Thr³⁰⁸)、磷酸化Akt(Ser⁴⁷³)和磷酸化GSK3β的表达变化。同时观察加入PI3K抑制剂——LY294002后内皮细胞的增殖情况。结果:与正常对照组（D-葡萄糖5mmol/L）相比,高糖明显抑制内皮细胞的增殖及磷酸化Akt(Thr³⁰⁸)和磷酸化GSK3β的表达,且抑制作用随其浓度增高而增强（P<0.05^P<0.01）。但高糖不影响内皮细胞中磷酸化Akt(Ser⁴⁷³)的表达（P>0.05）。LY294002抑制内皮细胞增殖,抑制作用随其浓度增高而增强（P<0.01）。渗透压改变不影响内皮细胞增殖（P>0.05）。结论:高糖可能通过PI3K-Akt信号途径抑制内皮细胞增殖,参与糖尿病大血管并发症的发生发展。更多还原

【Abstract】 Objective:To investigate the effect of high glucose on proliferation of endothelial cells and whether PI3K-Akt signaling pathway plays an important role in the pathogenesis of diabetic vascular complication.Methods:Proliferation data and expression of Akt,phosphorylated Akt(Thr³⁰⁸)(p-Akt(Thr³⁰⁸)),phosphorylated Akt(Ser⁴⁷³)(p-Akt(Ser⁴⁷³))and phosphorylated GSK3β（β-GSK3 β） of human umbilical vein endothelial cell were measured after exposured to various concentration of D-glucose,mannitol and PI3 K inhibitor—LY294002.Results:D-glucose at 15mmol/L and 30mmol/L dose-dependently decreased proliferation rate and the expression of p-Akt(Thr³⁰⁸)和p-GSKS β of endothelial cell versus control（P<0.05-P<0.01）,whereas mannitol did not influence the proliferation of endothelial cell（P>0.05）.Otherwise,high level D-glucose did not alter the expression of p-Akt(Ser⁴⁷³) in endothelial cell（P>0.05）.Pharmacological inhibition of PI3K-Akt resulted in dosedependent decrease of proliferation rate of endothelial cells（P<0.01）.Coaclusion:Hypeglycemia-impaired PI3K-Akt signaling may lead to dysfunction of endothelial cells proliferation in diabetes,which is likely to contribute to the pathogenesis of diabetic vascular complication.更多还原