Curcumin alleviates rheumatoid arthritis-induced inflammation and synovial hyperplasia by targeting mTOR pathway in rats
Curcumin alleviates rheumatoid arthritis-induced inflammation and synovial hyperplasia by targeting mTOR pathway in rats
复制标题
DOI：
10.2147/dddt.s175763
复制
发表时间：
2018-01-01
影响因子：
4.8
通讯作者：
Song, Xinwei
中科院分区：
文献类型：
--
作者：
Dai, Qiaoding;Zhou, Di;Song, Xinwei
目的：类风湿性关节炎（RA）是一种慢性进行性自身免疫性疾病，以侵袭性、对称性多发性关节炎为特征。哺乳动物雷帕霉素靶蛋白（mTOR）是治疗类风湿关节炎的新靶点，其抑制剂雷帕霉素可显著降低类风湿关节炎滑膜细胞的侵袭力。在这里，我们确定了姜黄素的效果，以减轻炎症和滑膜增生的治疗RA。材料和方法：胶原诱导的关节炎（CIA）在Wistar大鼠和作为一个类似RA在人类的模型。每天用姜黄素（200 mg/kg）和mTOR抑制剂雷帕霉素（2.5 mg/kg）处理大鼠3周。结果：姜黄素和雷帕霉素能显著抑制RA大鼠踝关节红肿，并能显著抑制关节肿胀，对关节局部、外周血及滑膜增生有明显的抑制作用。Curcinnin抑制CIA诱导的mTOR通路和RA诱导的炎性细胞向滑膜中的浸润。姜黄素和雷帕霉素治疗可抑制CIA大鼠中IL-1 β、TNF-α、MMP-1和MMP-3等促炎性细胞因子水平的升高。结论：姜黄素通过mTOR途径抑制CIA诱导的炎症、滑膜增生等CIA发病机制中的主要特征。这些结果为姜黄素的抗关节炎特性提供了证据，并证实了其用于治疗RA的潜在用途。
Purpose: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by aggressive and symmetric polyarthritis. Mammalian target of rapamycin (mTOR) was reported to be a new target for RA therapy and its inhibitor rapamycin can significantly reduce the invasive force of fibroblast-like synoviocytes. Here, we determined the effect of curcumin to alleviate inflammation and synovial hyperplasia for the therapy of RA.Materials and methods: Collagen-induced arthritis (CIA) was developed in Wistar rats and used as a model resembling RA in humans. Rats were treated with curcumin (200 mg/kg) and the mTOR inhibitor rapamycin (2.5 mg/kg) daily for 3 weeks. Effects of the treatment on local joint, peripheral blood, and synovial hyperplasia in the pathogenesis of CIA were analyzed.Results: Curcumin and rapamycin significantly inhibited the redness and swelling of ankles and joints in RA rats. Curcinnin inhibited the CIA-induced mTOR pathway and the RA-induced infiltration of inflammatory cells into the synovium. Curcumin and rapamycin treatment inhibited the increased levels of proinliammatory cytokines including IL-1 beta, TNF-alpha, MMP-1, and MMP-3 in CIA rats.Conclusion: Our findings show that curcumin alleviates CIA-induced inflammation, synovial hyperplasia, and the other main features involved in the pathogenesis of CIA via the mTOR pathway. These results provide evidence for the anti-arthritic properties of curcumin and corroborate its potential use for the treatment of RA.