Salvianolic Acid B Down-regulates Matrix Metalloproteinase-9 Activity and Expression in Tumor Necrosis Factor-α-induced Human Coronary Artery Endothelial Cells  

作　　者：Le Ma Yun-Qian Guan Zhong-Dong Du 

机构地区：[1]Department of Pediatrics,Beijing Children's Hospital,Capital Medical University,Beijing 100045,China [2]Cell Therapy Center,Beijing Institute of Geriatrics,Xuanwu Hospital of Capital Medical University,Beijing 100053,China

出　　处：《Chinese Medical Journal》2015年第19期2658-2663,共6页中华医学杂志（英文版）

基　　金：Acknowledgments We thank Medjaden and Editage for its linguistic assistance during the preparation of this manuscript. Financial support and sponsorship This study was supported by the grants from National Natural Science Foundation of China （No. 81274109, 30973238）, Key Research Project of Beijing Natural Science Foundation （B）/Beijing Education Committee （No. KZ201010025024）, and Project for Science and Technology Innovation, Beijing Education Committee （No. PXM2011 014226 07 000085）.

摘　　要：Background：Salvianolic acid B （Sal B） is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular diseases.This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 （MMP-9） and on the underlying mechanisms in tumor necrosis factor-α （TNF-α）-activated human coronary artery endothelial cells （HCAECs）,a cell model of Kawasaki disease.Methods：HCAECs were pretreated with 1 l0 μmol/L of Sal B,and then stimulated by TNF-α at different time points.The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay,respectively.Nuclear factor-κB （NF-κB） activation was detected with immunofluorescence,electrophoretic mobility shift assay,and Western blot assay.Protein expression levels of mitogen-activated protein kinase （c-Jun N-terminal kinase [JNK],extra-cellular signal-regulated kinase [ERK],and p38） were determined by Western blot assay.Results：After HCAECs were exposed to TNF-α,1-10 μtmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and activity.Furthermore,Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 min.In addition,Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 min.Conclusions：The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB,JNK,and ERK1/2 signaling pathways.Background：Salvianolic acid B （Sal B） is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular diseases.This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 （MMP-9） and on the underlying mechanisms in tumor necrosis factor-α （TNF-α）-activated human coronary artery endothelial cells （HCAECs）,a cell model of Kawasaki disease.Methods：HCAECs were pretreated with 1 l0 μmol/L of Sal B,and then stimulated by TNF-α at different time points.The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay,respectively.Nuclear factor-κB （NF-κB） activation was detected with immunofluorescence,electrophoretic mobility shift assay,and Western blot assay.Protein expression levels of mitogen-activated protein kinase （c-Jun N-terminal kinase [JNK],extra-cellular signal-regulated kinase [ERK],and p38） were determined by Western blot assay.Results：After HCAECs were exposed to TNF-α,1-10 μtmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and activity.Furthermore,Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 min.In addition,Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 min.Conclusions：The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB,JNK,and ERK1/2 signaling pathways.

关 键 词：Endothelial Cell Injury Kawasaki Disease Mitogen-activated Protein Kinase Matrix Metalloproteinase-9 Nuclear factor-κB Salvianolic Acid B 

分 类 号：Q513.5[生物学—生物化学] Q786