VEGF在类风湿关节炎滑液中的表达及上调MMP-2活性的研究

Expression of vascular endothelial cell growth factor and its upregulation of matrix metalloproteinase-2 activation in synovial fluid of patients with rheumatoid arthritis

目的探讨血管内皮生长因子(VEGF)在类风湿关节炎(RA)患者关节滑液中的表达及其上调基质金属蛋白酶-2(MMP-2)活性在RA关节损伤机制中的意义。方法采用免疫印迹法、酶联免疫吸附试验、明胶酶谱电泳分析法及侵袭小室法,观察RA患者组及对照组关节滑液单个核细胞中VEGF及受体KDR的表达,单个核细胞上清液中VEGF的水平,VEGF与KDR阳性的单个核细胞体外共培养前后上清中MMP-2的活性及细胞侵袭力的变化。结果VEGF及KDR在滑液单个核细胞高表达；共培养后MMP-2的活性及细胞的侵袭力明显增强。结论VEGF与受体KDR结合促使RA滑液单个核细胞MMP-2活性上调及细胞侵袭力的增强,促进受损关节软骨及骨的降解破坏。

Objective To investigate the expression of vascular endothelial cell growth factor （VEGF） and its upregulation of matrix metalloproteinase-2 （MMP-2） activation in synovial fluid of patients with rheumatoid arthritis （RA） as well as its role in the pathogeneses of RA. Mathods Expression of VEGF and receptor KDR in mononuclear cell （MNC） of synovial fluid of RA patients and controls were determined by Western blot; VEGF levels of supernantants from MNC was determined by ELISA; supernantants from KDR^＋ MNC of synovial fluid of RA patients collected after incubation in serum-free medium with or without VEGF, their activity of MMP-2 was measured by gelatinolytic zymography; Boyden chamher-matrigel in vitro invasion assay was used to detect the invasive capacity in vitro in KDR^＋ MNC of synovial fluid of RA patients incubated with or without VEGF. Results The expressions of VEGF/KDR in MNC of synovial fluid of RA patients were significantly higher than those of controls; the MMP-2 activity and invasive ability of co-cultured KDR^＋ MNC with VEGF was higher than those of without VEGF. Conclusion VEGF upregulates MMP-2 activation and promotes invasion of MNC of synovial fluid of RA patients by interacting with receptor KDR, indicating that VEGF plays an important role in RA pathology.