Abstract：
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, leading to severe inflammatory infiltration and joint damage, accompanied by a decrease in pH of joint microenvironment. Macrophages play an important role in the pathogenesis of RA, with high expression of bovine serum albumin (BSA) receptors on the surface of macrophages. Resveratrol (Res) has strong anti-inflammatory effects, but its application is limited due to its poor water solubility and low bioavailability. Therefore, we constructed pH-sensitive micelles by encapsulating Res and modifying BSA on the surface of the micelles (BSA-Res@Ms), thereby greatly improving the therapeutic effect of RA. Our research results indicated that BSA-Res@Ms had a smooth and uniform appearance, small particle size, high drug encapsulation efficiency, good stability, and pH-sensitive properties. In vitro, BSA-Res@Ms increased the uptake of Res by RAW264.7 cells, reduced the levels of pro-inflammatory cytokines and cleared excess ROS produced by activated RAW264.7 cells, and inhibited the generation of osteoclasts. In vivo, BSA-Res@Ms could target inflamed joint sites, significantly alleviate joint inflammation symptoms, inhibit activated macrophages, improve synovial hyperplasia and inflammatory cell infiltration, and protect cartilage. BSA-Res@Ms provide a very promising method for the treatment of RA, which can effectively improve the inflammatory manifestations of RA.
摘要：
类风湿性关节炎(RA)是一种慢性自身免疫性炎症性疾病,导致严重的炎症浸润和关节损伤，伴随着关节微环境pH值的降低。巨噬细胞在RA的发病机制中起着重要作用,巨噬细胞表面高表达牛血清白蛋白(BSA)受体。白藜芦醇（Res）具有很强的抗炎作用，但是由于其水溶性差和生物利用度低，其应用受到限制。因此,我们通过在胶束表面包裹Res和修饰BSA（BSA-Res@Ms）构建pH敏感胶束，从而大大提高RA的治疗效果。我们的研究结果表明，BSA-Res@Ms具有光滑均匀的外观，小粒径，药物包封效率高，稳定性好,和pH敏感特性。体外，BSA-Res@Ms增加RAW264.7细胞对Res的摄取，降低了促炎细胞因子的水平，清除了激活的RAW264.7细胞产生的过量ROS，并抑制破骨细胞的生成。在体内,BSA-Res@Ms可以瞄准发炎的关节部位，显著缓解关节炎症症状，抑制活化的巨噬细胞，改善滑膜增生和炎症细胞浸润，保护软骨.BSA-Res@Ms为治疗RA提供了一种非常有前途的方法，能有效改善RA的炎症表现。
