Inhibition of NET formation by polydatin protects against collagen-induced arthritis
Inhibition of NET formation by polydatin protects against collagen-induced arthritis
复制标题
虎杖甙抑制 NET 形成可预防胶原诱导的关节炎
DOI：
10.1016/j.intimp.2019.105919
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发表时间：
2019
影响因子：
5.6
通讯作者：
He Yi
中科院分区：
文献类型：
--
作者：
Yang Fangyuan;Luo Xiaoqing;Luo Guihu;Zhai Zeqing;Zhuang Jian;He Juan;Han Jiaochan;Zhang Yanan;Zhuang Lili;Sun Erwei;He Yi
背景风湿性关节炎（Rheumatoid arthritis，RA）是一种全身性、炎症性、自身免疫性疾病，可导致多种残疾.越来越多的证据表明，中性粒细胞胞外陷阱（NET）的形成在RA的发病和进展中起着重要作用。在这项研究中，我们的目的是探讨虎杖苷（PD）对NET的形成及其对疾病活动的影响，在胶原蛋白诱导的关节炎（CIA）小鼠model.MethodsIn存在的PD或车辆，中性粒细胞分离RA患者和小鼠用佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）处理4小时，和NET的形成调查。对于体内实验，腹膜内（45 mg/kg/天）向胶原诱导的关节炎（CIA）小鼠施用PD。胶原诱导的关节炎的发病率和严重程度进行了评估和NET deposition tested.ResultsIn体外，PD显着抑制从RA患者的中性粒细胞NET的形成。同时，在PD处理的骨髓源性中性粒细胞中观察到NET减少。在CIA小鼠模型中，PD治疗延迟了关节炎的发作并减轻了关节炎的严重程度。与车辆治疗的CIA小鼠相比，在踝关节的NET的沉积也减少PD治疗的CIA mice.ConclusionIn这项研究中，我们发现，PD治疗显着抑制NET的形成和保护CIA小鼠从关节炎的发展。这些结果表明，抑制NET形成PD可能作为一种新的机制，用于治疗RA。
BackgroundRheumatoid arthritis (RA) is a systematic, inflammatory, autoimmune disease, associated with a high number of disabilities. Increasing evidence has demonstrated that neutrophil extracellular trap (NET) formation plays a significant role in the pathogenesis and progression of RA. In this study, we have aimed to investigate the effects of polydatin (PD) on NET formation and its effects on disease activity in a collagen-induced arthritis (CIA) mouse model.MethodsIn the presence of PD or vehicle, neutrophils isolated from RA patients and mice were treated with phorbol 12-myristate 13-acetate (PMA) for 4 h, and NET formation investigated. For in vivo experiments, PD was administered intraperitoneally (45 mg/kg per day) to collagen-induced arthritis (CIA) mice. The incidence and severity of collagen-induced arthritis were assessed and NET deposition tested.ResultsIn vitro, PD significantly suppressed NET formation of neutrophils from RA patients. Consistently, decreased NETs were observed in PD treated bone marrow-derived neutrophils. In CIA mouse model, PD treatment delayed the onset of arthritis and attenuated arthritis severity. Compared with vehicle-treated CIA mice, the deposition of NETs in ankle joints was also reduced in PD-treated CIA mice.ConclusionIn this study, we found that PD treatment markedly inhibited NET formation and protected CIA mice from the development of arthritis. These findings suggest that inhibition of NET formation by PD may serve as a novel mechanism for the treatment of RA.