Zeng Ji-Zhou, Ma Li-Feng, Meng Hai, Yu Hao-Miao, Zhang Ya-Kui, Guo Ai
Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China; Department of Orthopaedics, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, P.R. China.
Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
Exp Ther Med. 2016 Nov;12(5):3101-3106. doi: 10.3892/etm.2016.3739. Epub 2016 Sep 21.
(5R)-5-hydroxytriptolide (LLDT-8) extracts from have anti-inflammatory, antineoplastic and immunity adjustment functions. The present study used a collagen-induced arthritis (CIA) model to evaluate whether LLDT-8 prevents collagen-induced arthritis, and investigated the signaling underlying this. Male Sprague-Dawley rats were induced to generate CIA, mimicking rheumatoid arthritis (RA). The presence of arthritis was determined using RA progression scores. The inflammatory cytokines interleukin (IL)-1β, IL-6 and nuclear factor-κB were detected using enzyme-linked immunosorbent assay kits. Induced nitric oxide synthase (iNOS) and matrix metalloprotease (MMP)-13 protein expression were measured using western blot analysis. Lastly, reverse transcription-quantitative polymerase chain reaction was used to evaluate osteoprotegerin (OPG) and receptor activator of nuclear factor κB (RANK) gene expression. LLDT-8 improved RA progression scores and reduced the incidence and severity of CIA. Furthermore, LLDT-8 administration inhibited collagen-induced inflammation and iNOS protein expression in arthritic rats. The current data indicated that MMP-13 production was suppressed and OPG/RANKL expression was increased by LLDT-8 treatment in the arthritic rat. The present results suggest that LLDT-8 attenuates CIA through OPG/RANK/RANK ligand signaling in a rat model of RA.
从[来源]中提取的(5R)-5-羟基雷公藤内酯醇（LLDT-8）具有抗炎、抗肿瘤和免疫调节功能。本研究使用胶原诱导性关节炎（CIA）模型来评估LLDT-8是否能预防胶原诱导性关节炎，并探究其潜在信号通路。雄性Sprague-Dawley大鼠被诱导产生CIA，模拟类风湿性关节炎（RA）。使用RA进展评分来确定关节炎的存在情况。使用酶联免疫吸附测定试剂盒检测炎性细胞因子白细胞介素（IL）-1β、IL-6和核因子-κB。使用蛋白质印迹分析来测量诱导型一氧化氮合酶（iNOS）和基质金属蛋白酶（MMP）-13的蛋白表达。最后，使用逆转录-定量聚合酶链反应来评估骨保护素（OPG）和核因子κB受体激活剂（RANK）基因的表达。LLDT-8改善了RA进展评分，降低了CIA的发病率和严重程度。此外，给予LLDT-8可抑制胶原诱导的关节炎大鼠炎症和iNOS蛋白表达。目前的数据表明，LLDT-8处理可抑制关节炎大鼠中MMP-13的产生，并增加OPG/RANKL的表达。本研究结果表明，在RA大鼠模型中，LLDT-8通过OPG/RANK/RANK配体信号通路减轻CIA。
