The aim of the article was to study the mechanism of Lipoxin A4 (LXA4)-mediated p38 MAPK pathway protecting mice against collagen-induced arthritis (CIA). The impact of LXA4 (0, 5, 10, 15 nM) on synoviocytes proliferation of CIA mice was detected using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. CIA mice were treated with LXA4, SB203580 (a p38 inhibitor), and/or anisomycin (a p38 agonist), and the arthritis severity score in each mouse was determined. The gene or protein expressions were detected with Western Blotting, ELISA, or qRT-PCR. LXA4 inhibited the synoviocytes proliferation of CIA mice with decreased levels of TNF-α, IL-6, IL-1β, and IFN-γ and reduced p-p38/total p38 expression in synoviocytes in a dose-dependent manner. LXA4 levels were decreased in synovial tissues and plasma of CIA mice, but p-p38/total p38 expression was increased in synovial tissues. LXA4 could downregulate p-p38/total p38 expression in synovial tissues of CIA mice. Both LXA4 and SB203580 reduced arthritis severity score of CIA mice with the reduction of synovial tissue hyperplasia and inflammatory cell infiltration. CIA mice treated with LXA4 and SB203580 had lower levels of TNF-α, IL-6, IL-1β, and IFN-γ, accompanying decreased MDA as well as increased SOD, CAT,and GPx. However, anisomycin could reverse the protect effects of LXA4 on CIA mice regarding the abovementioned inflammatory factors and oxidative stress indexes. LXA4 protected mice against collagen-induced arthritis via inhibiting p38 MAPK signaling pathway, which may be a potential new therapeutic target for rheumatoid arthritis.

本文的目的是研究脂氧蛋白A4（LXA4）介导的p38 MAPK途径保护小鼠免受胶原诱导的关节炎（CIA）的机制。使用3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT）分析检测到LXA4（0、5、10、15 nM）对CIA滑膜细胞增殖的影响。用LXA4，SB203580（p38抑制剂）和/或茴香霉素（p38激动剂）治疗CIA小鼠，并确定每只小鼠的关节炎严重程度评分。通过蛋白质印迹，ELISA或qRT-PCR检测基因或蛋白质表达。LXA4抑制CIA小鼠滑膜细胞增生，其TNF-α，IL-6，IL-1β和IFN-γ水平降低，滑膜细胞中p-p38 /总p38表达降低，且呈剂量依赖性。CIA小鼠滑膜组织和血浆中LXA4水平降低，但滑膜组织中p-p38 / p38的总表达增加。LXA4可以下调CIA小鼠滑膜组织中p-p38 / p38的表达。LXA4和SB203580均可通过降低滑膜组织增生和炎性细胞浸润来降低CIA小鼠的关节炎严重程度评分。用LXA4和SB203580处理的CIA小鼠的TNF-α，IL-6，IL-1β和IFN-γ含量较低，伴随MDA降低以及SOD，CAT和GPx升高。然而，关于上述炎症因子和氧化应激指标，茴香霉素可以逆转LXA4对CIA小鼠的保护作用。LXA4通过抑制p38 MAPK信号通路来保护小鼠免受胶原诱导的关节炎，这可能是类风湿关节炎的潜在新治疗靶点。LXA4可以下调CIA小鼠滑膜组织中p-p38 / p38的表达。LXA4和SB203580均可通过降低滑膜组织增生和炎性细胞浸润来降低CIA小鼠的关节炎严重程度评分。用LXA4和SB203580处理的CIA小鼠的TNF-α，IL-6，IL-1β和IFN-γ含量较低，伴随MDA降低以及SOD，CAT和GPx升高。然而，关于上述炎症因子和氧化应激指标，茴香霉素可以逆转LXA4对CIA小鼠的保护作用。LXA4通过抑制p38 MAPK信号通路来保护小鼠免受胶原诱导的关节炎，这可能是类风湿关节炎的潜在新治疗靶点。LXA4可以下调CIA小鼠滑膜组织中p-p38 / p38的表达。LXA4和SB203580均可通过降低滑膜组织增生和炎性细胞浸润来降低CIA小鼠的关节炎严重程度评分。用LXA4和SB203580处理的CIA小鼠的TNF-α，IL-6，IL-1β和IFN-γ含量较低，伴随MDA降低以及SOD，CAT和GPx升高。然而，关于上述炎症因子和氧化应激指标，茴香霉素可以逆转LXA4对CIA小鼠的保护作用。LXA4通过抑制p38 MAPK信号通路来保护小鼠免受胶原诱导的关节炎，这可能是类风湿关节炎的潜在新治疗靶点。LXA4和SB203580均可通过降低滑膜组织增生和炎性细胞浸润来降低CIA小鼠的关节炎严重程度评分。用LXA4和SB203580处理的CIA小鼠的TNF-α，IL-6，IL-1β和IFN-γ含量较低，伴随MDA降低以及SOD，CAT和GPx升高。然而，关于上述炎症因子和氧化应激指标，茴香霉素可以逆转LXA4对CIA小鼠的保护作用。LXA4通过抑制p38 MAPK信号通路来保护小鼠免受胶原诱导的关节炎，这可能是类风湿关节炎的潜在新治疗靶点。LXA4和SB203580均可通过降低滑膜组织增生和炎性细胞浸润来降低CIA小鼠的关节炎严重程度评分。用LXA4和SB203580处理的CIA小鼠的TNF-α，IL-6，IL-1β和IFN-γ含量较低，伴随MDA降低以及SOD，CAT和GPx升高。然而，关于上述炎症因子和氧化应激指标，茴香霉素可以逆转LXA4对CIA小鼠的保护作用。LXA4通过抑制p38 MAPK信号通路来保护小鼠免受胶原诱导的关节炎，这可能是类风湿关节炎的潜在新治疗靶点。和GPx。然而，关于上述炎症因子和氧化应激指标，茴香霉素可以逆转LXA4对CIA小鼠的保护作用。LXA4通过抑制p38 MAPK信号通路来保护小鼠免受胶原诱导的关节炎，这可能是类风湿关节炎的潜在新治疗靶点。和GPx。然而，关于上述炎症因子和氧化应激指标，茴香霉素可以逆转LXA4对CIA小鼠的保护作用。LXA4通过抑制p38 MAPK信号通路来保护小鼠免受胶原诱导的关节炎，这可能是类风湿关节炎的潜在新治疗靶点。