水煎剂通过调节 NF-κB 信号通路抑制破骨细胞生成来减轻胶原诱导性关节炎大鼠的骨侵蚀。

decoction attenuates bone erosion in rats that have collagen-induced arthritis via modulating NF-κB signalling to suppress osteoclastogenesis.

机构信息

School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

出版信息

Pharm Biol. 2021 Dec;59(1):262-274. doi: 10.1080/13880209.2021.1876100.

CONTEXT

decoction (GSZD) is commonly used to treat rheumatoid arthritis (RA), but its mechanism is unclear.

OBJECTIVE

To investigate the effect of GSZD on bone erosion in type II collagen (CII)-induced arthritis (CIA) in rats and to identify the underlying mechanism.

MATERIALS AND METHODS

The CIA model was prepared in male Wistar rats by two subcutaneous injections of CII, 1 mg/mL. Fifty CIA rats were randomized equally into the control group given saline daily, the positive group given saline daily and methotrexate 0.75 mg/kg once a week, and three GSZD-treated groups gavaged daily with 800, 1600 and 3200 mg/kg of GSZD for 21 days. GSZD effects were assessed by paw volume, arthritic severity index and histopathology. Cytokine levels were determined by ELISA. The effects of GSZD on RAW264.7 cells were evaluated by receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption assay. Expression of IκB-α and p65 was measured by Western blotting. Major components of GSZD were identified by HPLC.

RESULTS

Arthritis index score, paw volume and bone destruction score showed that GSZD improved inflammatory symptoms and reduced joint tissue erosion ( < 0.01). GSZD decreased RANKL, and the number of osteoclasts (OCs) in joint tissues ( < 0.01) and increased osteoprotegerin levels ( < 0.01). GSZD inhibited RANKL-induced RAW264.7 differentiation and reduced bone resorption by OCs. GSZD upregulated IκB ( < 0.01) and p65 ( < 0.01) in the cytoplasm and downregulated p65 ( < 0.01) in the cell nucleus.

CONCLUSIONS

decoction has an anti-RA effect, suggesting its possible use as a supplement and alternative drug therapy for RA.

背景

中药复方（GSZD）常用于治疗类风湿关节炎（RA），但其作用机制尚不清楚。

目的

探讨 GSZD 对Ⅱ型胶原（CII）诱导的关节炎（CIA）大鼠骨侵蚀的影响，并探讨其作用机制。

材料与方法

雄性 Wistar 大鼠通过两次皮下注射 1mg/ml 的 CII 制备 CIA 模型。将 50 只 CIA 大鼠随机均分为对照组（每日给予生理盐水）、阳性对照组（每日给予生理盐水和每周 1 次甲氨蝶呤 0.75mg/kg）和 3 个 GSZD 治疗组（每日分别灌胃给予 GSZD800、1600 和 3200mg/kg），共 21 天。通过爪体积、关节炎严重指数和组织病理学评估 GSZD 的作用。通过 ELISA 测定细胞因子水平。通过核因子-κB 受体激活剂配体（RANKL）诱导的破骨细胞形成和骨吸收试验评估 GSZD 对 RAW264.7 细胞的作用。通过 Western blot 测定 IκB-α和 p65 的表达。通过 HPLC 鉴定 GSZD 的主要成分。

结果

关节炎指数评分、爪体积和骨破坏评分表明，GSZD 改善了炎症症状，减少了关节组织侵蚀（ < 0.01）。GSZD 降低了关节组织中 RANKL 和破骨细胞（OCs）的数量（ < 0.01），并增加了骨保护素水平（ < 0.01）。GSZD 抑制了 RANKL 诱导的 RAW264.7 分化，并减少了 OCs 的骨吸收。GSZD 上调了细胞质中的 IκB（ < 0.01）和 p65（ < 0.01），并下调了细胞核中的 p65（ < 0.01）。