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脂氧素抑制关节炎大鼠滑膜及IL-1β刺激的RSC-364细胞中VEGF的表达

, PP. 2121-2125

Keywords: 类风湿性关节炎,佐剂诱导的关节炎,血管内皮生长因子,血管新生

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Abstract:

目的探讨在体内外脂氧素A4(lipoxinA4,LXA4)对血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)表达的影响及其可能机制。方法SD雄性大鼠(6~8周龄,200~250g,32只)分为正常对照组、BML-111单独处理组(BML-111)、佐剂诱导的关节炎(adjuvantarthritis,AA)模型组及BML-111干预组(AA+BML-111),每组8只。AA组通过左后足跖部注射弗氏完全佐剂诱导建立AA动物模型,AA+BML-111组于造模后每日腹腔注入LXA4受体激动剂BML-111。28d后,取病变关节滑膜组织,匀浆后ELISA法检测VEGF水平,免疫印迹法检测VEGF受体2(VEGFR2)总蛋白水平及磷酸化水平。体外培养RSC-364大鼠成纤维样滑膜细胞(fibroblast-likesynoviocyte,FLS),采用白细胞介素-1β(interleukin1β,IL-1β)诱导VEGF表达,加入空白溶剂或不同浓度LXA4(1~100nmol/L)共同孵育24h后,ELISA法检测上清液中VEGF水平,免疫印迹法检测P38、JNK和ERK的总蛋白水平及磷酸化水平,免疫印迹法检测缺氧诱导因子-1α(hypoxia-induciblefactors1α,HIF-1α)蛋白含量。结果在AA大鼠滑膜组织,BML-111明显降低VEGF水平(P<0.01),对VEGFR2表达无明显影响,但显著降低磷酸化VEGFR2的水平(P<0.01)。在FLS细胞,LXA4剂量依赖性抑制IL-1β诱导的VEGF表达(P<0.01),显著降低P38(P<0.05)、JNK和ERK磷酸化水平(P<0.01),下调HIF-1α含量(P<0.01)。结论LXA4可能通过抑制MAPK、HIF-1α下调RSC-364细胞中IL-1β诱导的VEGF表达,影响AA大鼠模型中血管新生和血管翳的形成。

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