天然产物研究与开发 ›› 2018, Vol. 30 ›› Issue (7): 1138-1142.doi: 10.16333/j.1001-6880.2018.7.007

所属专题: No.5

• 研究论文 • 上一篇    下一篇

齐墩果酸抑制肿瘤坏死因子-α诱导的成纤维细胞样滑膜细胞炎症因子表达及其机制研究

邓莉1,冯健2*,何成松1   

  1. 1西南医科大学附属医院风湿免疫科;2西南医科大学附属医院心血管内科,泸州 646000
  • 出版日期:2018-08-08 发布日期:2018-08-08
  • 基金资助:

    国家自然科学基金(31300946);泸州市-泸州医学院联合课题(2015LZCYD-S03)

Oleanolic Acid Inhibit Tumor Necrosis Factor Alpha-induced Inflammatory Cytokines Production of Synovial Cells and Its Mechanism

DENG Li1,FENG Jian2*,HE Cheng-song1   

  1. 1Department of rheumatology,the Affiliated Hospital of southwest Medical University; 2Department of Cardiology,the Affiliated Hospital of southwest Medical University,Luzhou 646000,China
  • Online:2018-08-08 Published:2018-08-08

摘要: 探讨齐墩果酸(Oleanolic acid,OA)对肿瘤坏死因子-α(TNF-α)诱导成纤维细胞样滑膜细胞的炎症因子表达的影响及其机制。首先复苏培养人成纤维细胞样滑膜细胞(FLS),通过RT-PCR检测细胞IL-6及IL-1β mRNA表达,采用Western blot方法检测p38MAPK及NF-κB蛋白表达变化,通过ELISA法检测细胞上清液中IL-6及IL-1β浓度。与对照组比较,TNF-α明显诱导FLS细胞IL-6及IL-1β mRNA的表达及上清液中IL-6及IL-1β的分泌(P< 0.05),同时磷酸化p38蛋白和核NF-κB明显增加(P< 0.05),且p38MAPK阻断剂SB203580能抑制TNF-α诱导的核NF-κB增加。OA呈浓度依赖性抑制TNF-α诱导的FLS细胞p38蛋白磷酸化和核NF-κB增加(P< 0.05)。且OA、p38MAPK通路抑制剂SB203580或NF-κB阻断剂BAY 11-7082均能抑制TNF-α诱导的IL-6及IL-1β分泌增加(P< 0.05)。综上所述,OA能抑制TNF-α诱导的FLS细胞炎症因子IL-6及IL-1β的产生,其机制可能与抑制p38MAPK/NF-κB信号通路有关。

关键词: 齐墩果酸, 滑膜细胞, 炎症因子, 肿瘤坏死因子-&alpha, , p38MAPK, NF-&kappa, B

Abstract: In the study,the effects of oleanolic acid(OA)on tumor necrosis factor alpha(TNF-α)-induced inflammatory cytokines production and the related mechanism in synovial cells were investigated.After culture of human fibroblast like synoviocytes(FLS),RT-PCR was used to detect the expression of IL-6 and IL-1β,and western blot method was used to detect the expression of p38 MAPK and NF-κB.ELISA was used to detect the levels of IL-6 and IL-1β in cell supernatant.Compared to control group,TNF-α significantly induced the production of IL-6 and IL-1β in FLS,increased the protein expression of P-p38MAPK and NF-κB(P< 0.05),and a p38MAPK antagonist SB203580 can inhibit TNF-α-induced the protein expression of NF-κB.OA concentration dependently inhibited TNF-α-induced protein expression of P-p38 MAPK and NF-κB in FLS cells.OA,a p38MAPK antagonist SB203580 or a NF-κB antagonist BAY 11-7082 can inhibit TNF-α-induced the production of IL-6 and IL-1β in FLS(P< 0.05).Collectively,these findings suggested that OA can inhibit TNF-α-induced the production of IL-6 and IL-1β,which may be through inhibiting p38MAPK/NF-κB pathway.

Key words: oleanolic acid, synoviocytes, inflammatory cytokines, tumor necrosis factor alpha, p38MAPK, NF-&kappa, B

中图分类号: 

R593.22