HIF-1α及VEGF在类风湿关节炎成纤维样滑膜细胞中的表达及意义  

Expression of HIF-1α and VEGF on fibroblast-like synoviocytes cells in patients with rheumatoid arthritis

作　　者：彭勇[1] 陈勇[1] 邬秀娣[1] 罗晶[2] 张振[1] 黄娴倩[1] 干敏芝[1] 

机构地区：[1]宁波市第二医院风湿免疫科,315010 [2]宁波市第六医院风湿免疫科

出　　处：《浙江医学》2013年第18期1628-1631,1643,共5页Zhejiang Medical Journal

基　　金：宁波市社会发展科研项目基金资助(2012C50010);宁波市自然基金项目资助(2013A610259)

摘　　要：目的研究类风湿性关节炎(RA)患者滑膜细胞在体外常氧和缺氧培养条件下缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)表达的差异性及意义。方法对RA患者及骨关节炎(OA)患者的关节滑膜细胞在体外常氧和缺氧条件下分别进行培养,根据培养条件分为常氧组、缺氧6h组及缺氧12h组;采用免疫印迹法分别检测各组成纤维样滑膜细胞的HIF-1α及VEGF的表达情况。结果与常氧组相比,缺氧6h及12h的RA和OA患者滑膜细胞的HIF-1α及VEGF的表达均显著增加,差异均有统计学意义(均P<0.05)。同时RA和OA患者缺氧12h组滑膜细胞HIF-1α及VEGF的表达高于缺氧6h组,差异均有统计学意义(均P<0.05)。RA和OA患者3组滑膜细胞的HIF-1α及VEGF的表达均呈正相关(均P<0.05)。常氧组RA与OA患者滑膜细胞的HIF-1α及VEGF的表达均无统计学差异(均P>0.05);而缺氧6h和12h组中RA滑膜细胞HIF-1α及VEGF的表达均高于OA滑膜细胞,差异均有统计学意义(均P<0.05)。结论在缺氧条件下RA患者滑膜细胞HIF-1α及VEGF表达显著升高且密切相关,可能缺氧一HIF-1α—VEGF这一信号途径在RA的发生、发展中起着重要作用。Objective To investigate the expression of hypoxia- inducible factor- 1α （HIF- 1α） and vascular endothelial growth factor （VEGF） on fibroblast- like synoviocytes cells in rheumatoid arthritis and its correlation with normoxia and hypoxia. Methods Primarily cultured fibroblast- like synoviocytes cells from patients with rheumatoid arthritis （RA） and osteoarthritis （OA） were exposed to normoxia for 6h or hypoxia for 6h and 12h. The expression of HIF- 1αand VEGF were detected by Western blot. Results The expressions of HIF- 1α and VEGF in fibroblast- like synoviocytes cells from RA or OA patients exposed to hypoxia for 6h and 12h were higher than those exposed to normoxia（P〈0.05）. Compared to those exposed to hypoxia for 6h, the expres-sion of HIF- 1α and VEGF in cells exposed to hypoxia for 12h was higher （P〈0.05）. The expression of HIF- 1α was positively correlated with VEGF in three groups （P〈0.05）. The expressions of HIF- 1αand VEGF in fibroblast- like synoviocytes cells from RA patients exposed to hypoxia for 6h and 12h were higher than those from OA patients correspondingly （P〈0.05）, however, there were no significant difference in normoxic group between RA and OA patients（P〉0.05）. Conclusion In hypoxia conditions the expressions of HIF- 1α and VEGF on fibroblast- like synoviocytes cells from RA patients are significantly higher than those from OA patients, indicating that Hypoxia-HIF- 1α-VEGF signaling pathway may be closely related to the occurrence and de-velopment of RA.

关 键 词：类风湿性关节炎 骨关节炎 滑膜细胞 缺氧诱导因子- 1α 血管内皮生长因子 

分 类 号：R593.22[医药卫生—内科学]