Feng Wei, Wan Xin, Fan Shirong, Liu Cui-Zhen, Zheng Xue-Xia, Liu Qing-Ping, Liu Min-Ying, Liu Xiao-Bao, Lin Chang-Song, Zhang Li-Juan, Li De-Tang, Xu Qiang
The First Clinical Medicine School, Guangzhou University of Chinese Medicine. Guangzhou 510405, China.
Department of Rheumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine. Guangzhou 510405, China.
Heliyon. 2023 Apr 29;9(5):e15867. doi: 10.1016/j.heliyon.2023.e15867. eCollection 2023 May.
Rheumatoid arthritis (RA) is a chronic immune disease characterised by synovitis and cartilage destruction. Currently, many patients experience poor remission after new antirheumatic drug treatments. Duanteng-Yimu Tang (DTYMT), a traditional Chinese medicine, is effective in the treatment of RA. In this research, we designed to investigate the anti-RA effects of DTYMT and explore its potential mechanisms.
Network pharmacology was adopted to explore the main pathways of DTYMT in patients with RA. Collagen-induced arthritis models of male DBA/1 mice were established, and their histopathological changes were observed by hematoxylin-eosin staining and micro-CT. qRT-PCR was performed to detect the expression of Foxp3 and RORγt in the serum and synovial tissue and IL-17, IL-1β, TNF-α, and IL-10 mRNA in vivo. The proliferation and invasion of synovial cells were analyzed using Cell Counting Kit-8 and transwell assays, respectively. The ratio of T helper 17 (Th17) to regulatory T (Treg) cells was analyzed by flow cytometry.
Network pharmacology analysis revealed that Th17 cell differentiation may be the key pathway of DTYMT in RA. DTYMT ameliorated joint damage, inhibited RORγt expression, and increased Foxp3 expression in CIA mice. DTYMT significantly decreased IL-1β, IL-17, and TNF-α mRNA levels, and increased IL-10 mRNA levels in IL-6-induced cells. Additionally, DTYMT inhibited Th17 cell differentiation and promoted Treg cell production, thus improving the Treg/Th17 imbalance. DTYMT also inhibited the proliferation, migration, and invasion of RA fibroblast-like synovial cells.
These results indicate that DTYMT could regulate the Treg/Th17 cell balance, which is a possible mechanism of DTYMT in treating RA.
类风湿关节炎（RA）是一种以滑膜炎和软骨破坏为特征的慢性免疫疾病。目前，许多患者在接受新型抗风湿药物治疗后缓解情况不佳。中药方剂“断藤益母汤”（DTYMT）在RA治疗中具有疗效。在本研究中，我们旨在探究DTYMT的抗RA作用并探索其潜在机制。
采用网络药理学方法探究DTYMT治疗RA患者的主要途径。建立雄性DBA/1小鼠胶原诱导性关节炎模型，通过苏木精-伊红染色和显微CT观察其组织病理学变化。采用qRT-PCR检测血清和滑膜组织中Foxp3和RORγt的表达以及体内IL-17、IL-1β、TNF-α和IL-10 mRNA的表达。分别使用细胞计数试剂盒-8和Transwell实验分析滑膜细胞的增殖和侵袭能力。通过流式细胞术分析辅助性T细胞17（Th17）与调节性T（Treg）细胞的比例。
网络药理学分析显示，Th17细胞分化可能是DTYMT治疗RA的关键途径。DTYMT改善了CIA小鼠的关节损伤，抑制了RORγt表达，并增加了Foxp3表达。DTYMT显著降低了IL-6诱导细胞中IL-1β、IL-17和TNF-α mRNA水平，并增加了IL-10 mRNA水平。此外，DTYMT抑制Th17细胞分化并促进Treg细胞生成，从而改善Treg/Th17失衡。DTYMT还抑制了RA成纤维样滑膜细胞[注1] 的增殖、迁移和侵袭。
这些结果表明，DTYMT可调节Treg/Th17细胞平衡，这可能是DTYMT治疗RA的机制。
[注1] 这里的“RA fibroblast-like synovial cells”直译为“类风湿关节炎成纤维样滑膜细胞”，为使译文更通顺，调整为“RA成纤维样滑膜细胞”。
