【摘要】 该文旨在明确藜麦源三萜(CQWT)对类风湿性关节炎(RA)潜在的干预作用。该研究首先采用CCK8和EdU法检测了CQWT对RA-FLS细胞增殖的影响;其次通过集落形成实验评估了RA-FLS的克隆形成能力;随后通过流式细胞术检测了细胞凋亡情况,并采用Western blot检测了凋亡蛋白的表达情况;再次通过伤口愈合和Transwell实验评估了CQWT对RA-FLS细胞迁移侵袭能力的影响,同时通过qPCR和Western blot检测了EMT相关蛋白的表达情况;接着又采用ELISA分析了炎症因子分泌水平;最后构建CIA小鼠,评估了CQWT对关节炎症状、血清炎症因子水平及滑膜病理改变的影响。体外实验结果显示, CQWT显著抑制RA-FLS增殖和集落形成,并通过上调Caspase-3表达诱导细胞凋亡。同时, CQWT通过增加E-cadherin表达水平,下调N-cadherin和Vimentin的表达,从而抑制RA-FLS迁移和侵袭。此外, CQWT能显著抑制RA-FLS细胞中TNF-α、IL-6和IL-1β的分泌。体内实验结果表明, CQWT可显著降低CIA小鼠关节炎指数,降低血清炎症因子水平,减轻滑膜增生和关节组织病理损伤,进而改善RA。总之,藜麦麸皮中三萜类化合物可通过抑制RA-FLS的异常增殖和迁移侵袭,诱导其凋亡并减轻炎症反应,从而延缓RA的病理进程。这些发现为藜麦源三萜在RA干预中的潜在应用提供了理论基础。更多还原

【Abstract】 This work was to investigate the potential therapeutic effects of the CQWT(Chenopodium quinoa Willd triterpenoid) on RA(rheumatoid arthritis). Here, the cell proliferation of RA-FLS(rheumatoid arthritis fibroblast-like synoviocytes) was evaluated using CCK8 and EdU assays, and clonogenic capacity was assessed by colony formation assays. Apoptosis was analyzed by flow cytometry, and the expression of apoptosis-related proteins was determined through Western blot. The effects of CQWT on RA-FLS migration and invasion were examined using wound healing and Transwell assays, while the expression of EMT(epithelial-mesenchymal transition)-related markers was analyzed by qPCR and Western blot. Inflammatory cytokine secretion was measured through ELISA. In addition, a CIA(collagen-induced arthritis) mouse model was established to evaluate the effects of CQWT on arthritis severity, serum inflammatory cytokine levels, and synovial pathological alterations. In vitro results demonstrated that CQWT significantly inhibited RA-FLS proliferation and colony formation and induced apoptosis through upregulation the Caspase-3 expression. Meanwhile, RA-FLS migration and invasion were markedly suppressed by CQWT, accompanied by increased E-cadherin expression and decreased expression of N-cadherin and Vimentin. Furthermore, the secretion of TNF-α, IL-6, and IL-1β in RA-FLS was significantly reduced following CQWT treatment. In vivo, CQWT administration significantly decreased arthritis scores in CIA mice, suppressed serum inflammatory cytokine levels, and alleviated synovial hyperplasia and joint pathological damage, thereby ameliorating RA progression. In conclusion, triterpenoid compounds derived from quinoa bran were shown to ameliorate RA-associated pathological progression through inhibiting abnormal RA-FLS proliferation, migration, and invasion, inducing apoptosis, and attenuating inflammatory responses. These findings provide a theoretical basis for the potential application of quinoa-derived triterpenoids in RA prevention and intervention.更多还原