PGN刺激对低氧诱导RASF表达VEGF的影响

Effect of PGN stimulation on hypoxia-induced VEGF expression in RASF

目的 观察TLR2配体肽聚糖（PGN）刺激对低氧诱导类风湿关节炎滑膜成纤维细胞（RASF）表达低氧诱导因子1 α（HIF-1 α）和血管内皮生长因子（VEGF）的影响.方法 分离RASF 6例,建立体外培养体系,将RASF分为对照组、CoCl2组、PGN组和CoCl2＋PGN组,qRT-PCR检测HIF-1 α表达,ELISA检测VEGF表达,siHIF-1 α后ELISA检测VEGF表达.结果 CoCl2组RASF表达HIF-1 α和VEGF水平高于对照组（P＜0.05）,PGN刺激能明显增强CoGl2诱导RASF表达HIF-1 α和VEGF的水平（P＜0.05）,干扰HIF-1 α后明显下调PGN协同CoCl2诱导RASF产生VEGF的效应（P＜0.05）.结论 TLR2信号激活能明显增强低氧诱导RASF产生VEGF的能力,干扰HIF-1 α是RA治疗的有效策略.

Objective To investigate the effect of peptidoglycan （PGN） on the expression of hypoxia-inducible factor-1 α （HIF-1 α） and vascular endothelial growth factor （VEGF） in rheumatoid arthritis synovial fibroblast （RASF） induced by hypoxia.Methods RASF were isolated from 6 cases of rheumatoid arthritis （RA） and cultured in vitro,then divided into control group,CoCl2 group,PGN group and CoCl2 ＋ PGN group.The mRNA level of HIF-1 α was detected by qRT-PCR and then the protein level of VEGF was tested by ELISA before and after silencing HIF-1 α.Results The expression of HIF-1 α and VEGF was upregulated in RASF induced by CoCl2 compared to control （P 〈 0.05）.PGN potentiated the levels of HIF-1 α and VEGF in RASF treated by CoCl2 （P 〈 0.05）.Silencing HIF-1 α decreased PGN and hypoxia-augmented VEGF production （P 〈 0.05）.Conclusion Activation of TLR2 signaling can enhance the levels of HIF-1 α and VEGF in RASF under hypoxia environment,and interfereing of HIF-1 α may be an effective therapeutic strategy for RA.