NADPH氧化酶参与机械牵张大鼠血管平滑肌细胞MCP-1 mRNA的生成

Cyclic Mechanica Stretch Enhances MCP-1 mRNA Expression via Activation of NADPH Oxidase in Vascular Smooth Muscle Cells

目的研究周期性机械牵张力对大鼠血管平滑肌细胞(VSMCs)产生单核细胞趋化蛋白1(MCP-1)mRNA的影响以及NADPH氧化酶在此过程中的作用。方法将培养的大鼠VSMCs种植于覆有胶原Ⅰ的BioFlex 6孔培养皿中,分为对照组(C组)、机械牵张组(ST组)和机械牵张+二苯基氯化碘盐预处理组(ST+DPI组),ST组及ST+DPI组采用Flexercell 3000系统给予能使细胞20%的纵向拉伸、频率60次/min的周期性机械牵张力,观察各组细胞MCP-1 mRNA的表达、超氧阴离子的产生以及NADPH氧化酶的胞质亚基P47phox的膜转位表达。结果周期性机械牵张力明显增加VSMCs产生MCP-1 mRNA及超氧阴离子,伴有NADPH氧化酶的亚基P47phox的膜转位表达增加;DPI通过减少P47phox的膜转位表达抑制NADPH氧化酶从而减少超氧阴离子产生,进一步减少MCP-1 mRNA表达。结论机械牵张能活化VSMCs的NADPH氧化酶,通过增加超氧阴离子的形成增加MCP-1 mRNA的生成。

Objective To investigate the effects of cyclic mechanical stretch on the expression of monocyte chemoattractant protein-1（MCP-1） mRNA in the rats vascular smooth muscle cells（VSMCs） and the role of NADPH oxidase in the process.Methods VSMCs were cultured on flexible silicone membranes and exposed to cyclic mechanical stretch and cyclic mechanical stretch plus DPI（inhibitor of NADPH oxidase） respectively.MCP-1 mRNA,superoxide ion and P47phox membrane translocation were detected.Results Cyclic mechanical stretch enhanced the expression of MCP-1 mRNA and production of superoxide ion and membrane translocation of P47phox,DPI down-regulated the expression of MCP-1 mRNA and production of superoxide ion via inhibition of P47phox membrane translocation.Conclusion Cyclic mechanical stretch can activate NADPH oxidase and augment production of superoxide ion,and further promote the production of MCP-1 mRNA in VSMCs.