Therapeutic effects of benzoylaconitine and paeoniflorin in rats with collagen-induced arthritis

Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1β, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1β, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination.

摘要 本研究旨在探讨苯甲酰乌头原碱（benzoylaconitine）与芍药苷（paeoniflorin）对胶原诱导性关节炎（collagen-induced arthritis, CIA）模型大鼠的作用及机制。在CIA造模诱导完成后，对各组大鼠的体重、足肿胀度、关节炎指数及关节病理变化进行检测。采用酶联免疫吸附测定（enzyme-linked immunosorbent assay, ELISA）检测血清中前列腺素E2（PGE2）、白细胞介素1β（IL-1β）、白细胞介素6（IL-6）、白细胞介素10（IL-10）、肿瘤坏死因子α（TNF-α）、血管内皮生长因子（VEGF）、基质金属蛋白酶3（MMP-3）、免疫球蛋白G（IgG）及抗Ⅱ型胶原抗体（anti-CII Ab）的水平；通过免疫组化法分析信号转导与转录激活因子1（signal transducer and activator of transcription 1, STAT1）和信号转导与转录激活因子3（signal transducer and activator of transcription 3, STAT3）的表达情况，并借助透射电子显微镜观察滑膜细胞的超微结构。本研究通过向CIA模型大鼠注射苯甲酰乌头原碱与芍药苷评估其治疗效果，结果显示：二者可减轻足肿胀程度与关节炎指数（AI），改善骶髂腺病理损伤；降低血清中PGE2、IL-1β、TNF-α、VEGF及IgG的水平；下调滑膜组织中STAT1与STAT3的蛋白表达；并抑制滑膜细胞的分泌与增殖活性。上述结果表明，苯甲酰乌头原碱与芍药苷可显著缓解CIA模型大鼠的关节炎症状，且二者联合使用可获得更优的治疗效果。