TLR4/NF-κB信号通路在ox-LDL诱导的血管平滑肌细胞分泌MCP-1中的作用  

Role of TLR4/NF-κB signaling pathway on MCP-1 secretion induced by ox-LDL in vascular smooth muscle cells

作　　者：徐斌[1] 张延斌[2] 张春华[1] 陈琰[1] 樊仁红[1] 殷宇[1] 许旭光[2] 

机构地区：[1]江苏省原子医学研究所附属江原医院内科,卫生部核医学重点实验室/江苏省分子核医学重点实验室,江苏无锡市214000 [2]徐州医学院附属医院心内科

出　　处：《心血管康复医学杂志》2013年第3期215-218,F0003,共5页Chinese Journal of Cardiovascular Rehabilitation Medicine

摘　　要：目的:探讨Toll样受体4/核因子-κB(TLR4/NF-κB)信号通路在氧化性低密度脂蛋白(ox-LDL)诱导的血管平滑肌细胞(VSMCs)分泌单核细胞趋化因子-1(MCP-1)中的作用。方法:取SD大鼠胸主动脉中膜培养血管平滑肌细胞,以2.5mg/L、5.0mg/L、10.0mg/L的TLR4中和抗体(TLR4阻断剂)、5μmol/L、10μmol/L、、20μmol/LPDTC(NF-κB特异性阻断剂)分别进行干预,并分别设置空白对照组和ox-LDL组,观察其对血管平滑肌细胞中ox-LDL诱导的MCP-1表达的影响。结果:与空白对照组比较,ox-LDL组VSMCs MCP-1mRNA及蛋白的表达明显升高(P<0.05);与ox-LDL组比较,用TLR4中和抗体预孵育后Anti-TLR4三组MCP-1mRNA[(1.23±0.21)比(0.81±0.02)、(0.75±0.01)、(0.49±0.01)]及其蛋白的表达[(0.64±0.05)ng/ml比(0.41±0.12)ng/ml、(0.32±0.07)ng/ml、(0.21±0.02)ng/ml]明显降低(P均<0.01),且呈浓度依赖性;用PDTC预孵育后PDTC三组MCP-1mRNA[(1.37±0.19)比(1.02±0.08)、(0.87±0.01)、(0.56±0.02)]及其蛋白的表达[(0.65±0.07)ng/ml比(0.51±0.07)ng/ml、(0.30±0.08)ng/ml、(0.19±0.02)ng/ml]亦明显降低(P均<0.01),且呈浓度依赖性。结论:氧化性低密度脂蛋白是TLR4的内源性配体;氧化性低密度脂蛋白通过或部分通过TLR4/NF-κB信号通路介导血管平滑肌细胞单核细胞趋化因子-1的表达。Objective：To explore role of Toll-like receptor 4/nuclear factor-κB（TLR4/NF-κB） signaling pathway on secretion of monocyte chemoattractant protein-1（MCP-1） induced by oxidized low density lipoprotein（ox-LDL） in vascular smooth muscle cells（VSMCs）.Methods：Thoracic aorta media of SD rat was taken to culture VSMCs.VSMCs were intervened by different concentrations of TLR4neutralizing antibodies（TLR4blocker,2.5mg/L、5.0mg/L、10.0mg/L） and PDTC（NF-κB specific blocker,5μmol/L、10μmol/L 、、20μmol/L）.The blank control group and ox-LDL group were set respectively.Their influences on MCP-1expression induced by ox-LDL in VSMCs were observed.Results：Compared with blank control group,there were significant increase in expressions of VSMCs MCP-1mRNA and protein in ox-LDL group,P0.05;compared with ox-LDL group after TLR4neutralizing antibody preincubation,there were significant decrease in expressions of MCP-1mRNA [（1.23±0.21） vs.（0.81±0.02）,（0.75±0.01）,（0.49±0.01）] and protein [（0.64±0.05） ng/ml vs.（0.41± 0.12） ng/ml,（0.32±0.07） ng/ml,（0.21±0.02） ng/ml ] in three Anti-TLR4groups（P〈0.01all）,and it′s concentration-dependent;After PDTC preincubation,there were also significant decrease in expressions of MCP-1 mRNA [（1.37±0.19） vs.（1.02±0.08）,（0.87±0.01）,（0.56±0.02）] and protein [（0.65±0.07） ng/ml vs.（0.51±0.07） ng/ml,（0.30±0.08） ng/ml,（0.19±0.02） ng/ml ] in three PDTC groups（P0.01all）,and it′s al-so concentration-dependent.Conclusion：The oxidized low density lipoprotein is an endogenous ligand of TLR4.Expression of monocyte chemoattractant protein-1in vascular smooth muscle cells is induced by oxidized low density lipoprotein through TLR4/NF-κB signaling pathway mediation partially or completely.

关 键 词：脂蛋白类 LDL 单核细胞化学吸引蛋白质1 NF-ΚB 肌 平滑 血管 

分 类 号：Q813.110.9[生物学—生物工程]