甘草苷素通过抑制炎症和纤维化,减轻了小鼠胶原诱导的关节炎和心脏并发症。
Liquiritigenin Attenuated Collagen-Induced Arthritis and Cardiac Complication via Inflammation and Fibrosis Inhibition in Mice.
发表日期:2023
作者:
Xiaoran Ning, Yanhui Ni, Jingjing Cao, Huaxing Zhang
来源:
Arthritis & Rheumatology
摘要:
类风湿性关节炎(RA)是一种常见的自身免疫性疾病,具有增加心血管疾病风险的特点。甘草苷素(LG)是一种具有抗炎作用的三萜类化合物。我们的研究旨在探讨LG对RA和心脏并发症的影响。经LG治疗的胶原诱导性关节炎(CIA)小鼠表现出明显的组织病理学变化缓解,伴随着滑膜和血清中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6和IL-17A表达的下降。LG通过降低CIA小鼠滑膜中基质金属蛋白酶(MMP)-3和MMP-13的表达,减轻了软骨破坏。超声心动图结果证明了LG缓解CIA小鼠心脏功能障碍的效果。心电图、生化和组织化学分析证明了LG对RA的心脏保护作用。CIA小鼠心脏组织中炎症因子(TNF-α、IL-1β和IL-6)和纤维化标志物(纤连蛋白、胶原蛋白I和III)表达的降低进一步证实了LG通过减轻心肌炎症和纤维化来减轻心脏并发症。机制研究表明,LG能够抑制CIA小鼠心脏组织中转化生长因子β-1(TGF-β1)和phos-Smad2/3的表达。我们的研究提示,LG可以通过抑制TGF-β1/Smad2/3通路来缓解RA及其心脏并发症。所有这些表明,LG可能是治疗RA及其心脏并发症的潜在候选药物。
Rheumatoid arthritis (RA) is a common autoimmune disease with increased cardiovascular disease risk. Liquiritigenin (LG) is a triterpene with anti-inflammatory properties. Our study aimed to explore the effect of LG on RA and the cardiac complication. Collagen-induced arthritis (CIA) mice with LG treatment exhibited obvious alleviation in histopathological changes, accompanied by the decreased expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-17A in synovium and serum. LG attenuated cartilage destruction by reducing matrix metalloproteinase (MMP)-3 and MMP-13 expression in the synovium of CIA mice. The echocardiography results proved the alleviation of cardiac dysfunction in CIA mice. The electrocardiogram, biochemical, and histochemical analysis proved the cardioprotection effect of LG against RA. The decreased expression of inflammatory factors (TNF-α, IL-1β, and IL-6) and fibrotic markers (fibronectin, Collagen I, and Collagen III) in cardiac tissues of CIA mice further corroborated the attenuation of myocardial inflammation and fibrosis by LG. Mechanistic studies showed that LG could inhibit transforming growth factor β-1 (TGF-β1) and phos-Smad2/3 expression in cardiac tissues of CIA mice. Our study suggested that LG could relieve RA and its cardiac complication probably by inhibiting the TGF-β1/Smad2/3 pathway. All these suggested that LG might be a potential candidate for RA and its cardiac complication therapy.