丝裂原活化蛋白激酶在染料木黄酮抑制血管内皮细胞中的作用  

The role of MAPK in inhibition of vascular endothelial cell induced by genistein

作　　者：余小平[1] 程道梅[1] 彭晓莉[1] 贾皓[1] 韩彬[1,2] 

机构地区：[1]成都医学院公共卫生系,四川成都610083 [2]遵义医学院公共卫生学院,贵州遵义563003

出　　处：《成都医学院学报》2011年第3期186-191,共6页Journal of Chengdu Medical College

基　　金：国家自然科学基金(No:30972462);四川省科技厅青年基金(No:09ZQ026-036);成都医学院重点项目(No:CYZ07-001)

摘　　要：目的探讨染料木黄酮(genistein,Gen)抑制血管内皮细胞的分子机制。方法人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)经血管内皮生长因子(VEGF)预处理后,给予1、10、100μmol/Gen,利用酶链免疫吸附测定(ELISA)法检测基质金属蛋白酶-2/-9(matrix metalloproteinase-2/-9,MMP-2/9)及其抑制剂基质金属蛋白酶抑制因子(TIMP-)2/9的表达,蛋白免疫印迹法检测丝裂原活化蛋白激酶(MAPK)表达,胶原蛋白酶分析试剂盒检测溶胶原和明胶分解活性。结果 VEGF能促进HUVECs MMP-2/9的分泌和活性,上调氨基端激酶(JNK)和p38表达。Gen能降低MMP-2/9的分泌和活性,下调JNK和p38表达。结论 Gen可通过抑制MAPK活性,减少MMPs的生成,从而阻断VEGF诱导的内皮细胞活化。Objective To investigate the molecular mechanism underlying the activation inhibition of vascular endothelial cell induced by genistein.Methods The human umbilical vein endothelial cells（HUVECs） were treated with genistein of 1,10,100 μmol/L after treated with vascular endothelial grouth factor（VEGF）,then the expression of（MMP-2/-9 and TIMP-2/-9 were analyzed by ELISA method,MAPK expression（JNK,p38,ERK1/2） was detected with Western blot,and the collagenolytic and gelatinolytic activity were measured with collagenase assay kit and type IV collagenase assay kit.Results Stimulation of HUVECs by VEGF augmented matrix metalloproteinase-2/-9（MMP-2/-9） secretions and increased MMP-2/-9 activities,up-regulated the JNK and p38 expression.Treatment of ECs with genistein decreased production and inhibited activity of matrix metalloproteinases（MMP-2/-9）,and down-regulated the JNK and p38 expression.Conclusions Genistein interrupt the VEGF-sitmulated endothelial cell activation through inactivating MAPK,and decreasing the production of MMPs.

关 键 词：染料木黄酮 血管内皮生长因子 人脐静脉内皮细胞 丝裂原活化蛋白激酶 

分 类 号：R151.2[医药卫生—营养与食品卫生学]