脂联素对体外培养人类风湿关节炎滑膜成纤维细胞合成MMP-3的影响

Effect of Adiponectin on the Synthesis of MMP-3 in Human Synovial Fibroblasts of Rheumatoid Arthritis in Vitro

目的:探讨脂联素对类风湿关节炎(RA)滑膜成纤维细胞合成分泌MMP-3的影响机制。方法:购买培养类风湿关节炎滑膜成纤维细胞(MH7A),给予脂联素刺激,观察不同浓度及时间下MMP-3mRNA及蛋白的合成分泌情况;随后通过NF-κB抑制剂检测最常见的炎性通路NF-κB是否参与了本调控;最后采用慢病毒基因沉默的手段,检测NF-κB通路的亚基p65和IKKβ的参与情况。结果:脂联素促进人滑膜成纤维细胞中MMP-3mRNA和蛋白的表达,并呈时间、剂量依赖效应。脂联素是通过NF-κB通路参与调控人滑膜成纤维细胞中MMP-3的表达,NF-κB通路中p65和IKKβ介入了脂联素对MMP-3的调控。结论:脂联素通过NF-κB(p65,IKKβ)通路促进类风湿关节炎滑膜成纤维细胞MMP-3的表达,提示脂联素可能为RA的前炎性因子,参与了RA的发生发展。

Objective：To investigate the effect of adiponectin on the synthesis and secretion of MMP-3 in synovial fibroblasts of rheumatoid arthritis.Methods：The synovial fibroblasts（MH7A）of rheumatoid arthritis were stimulated by adiponectin.The synthesis and secretion of MMP-3 mRNA and protein were observed under different concentrations and time points.The NF-κB inhibitor was used to detect if the NF-κB,one of common inflammatory signal pathway,was involved the regulation.The slow virus gene silencing methods were used to detect the participation of p65 and IKKβ,the subunit of NF-κB.Results：Adiponectin promoted the expression of MMP-3 mRNA and protein in human synovial fibroblasts,and it was time and dose dependent effect.Adiponectin was involved in the regulation of MMP-3 expression in human synovial fibroblasts by NF-κB signal pathway,and the p65 and IKKB were involved too.Conclusion：Adiponectin can promote the expression of MMP-3 in synovial fibroblasts of rheumatoid arthritis by NF-κB signal pathway,which suggesting that adiponectin may be a proinflammatory factor and involved in the development of rheumatoid arthritis.