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补肾通络方通过抑制胶原诱导性关节炎(CIA)大鼠的NF-κB/RANK/RANKL通路减轻骨破坏

[Bushentongluo recipe (BSTL) attenuates bone destruction by inhibiting NF-κB/RANK/RANKL pathway in collagen-induced arthritis (CIA) rats].

作者信息

Liu Hailong, Wang Gang, Wang Jia, Wang Tao, Tian Jiexiang, Wang Liqin, Yang Fang

机构信息

Department of Rheumatology and Bone Disease, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China.

Department of Rheumatology and Bone Disease, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China. *Corresponding author, E-mail:

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2021 Mar;37(3):205-211.

Abstract

Objective To investigate the therapeutic effect of Bushentongluo recipe (BSTL) on bone destruction and its inhibiting effect on NF-κB/RANK/RANKL pathway in collagen-induced arthritis (CIA) rats. Methods SD rats were randomly divided into blank control group, CIA model group, methotrexate (MTX, 1 mg/kg) group, BSTL 0.5 g/kg and 2 g/kg groups, with 10 rats in each. Except the control group, the other rats were injected subcutaneously with type 2 collagen(Col2) at the base of the tail to establish CIA models. After exposure to MTX or BSTL recipe for consecutive 28 days, the pathological change of joint tissues was examined by HE staining. Immunohistochemistry was used to detect NF-κB p65 expression in synovial tissues. The cytokines and anti-Col2 levels were analyzed by ELISA. Western blotting was used to detect the expression of RANKL, RANK and osteoprotegerin (OPG) proteins. Results Compared with the CIA model group, the rats treated with 2 g/kg BSTL for 28 days had lower paw volume, arthritis index (AI), serum levels of IL-1β, IL-18, TNF-α, anti-Col2-IgG, anti-Col2-IgG2a, RANK and RANKL, and higher level of serum OPG. Besides, Western blotting showed that the expression of NF-κB p65, RANK and RANKL proteins decreased, but the expression of OPG protein increased in BSTL 2 g/kg group. Conclusion BSTL can alleviate the rheumatoid arthritis by down-regulating the expression of NF-κB p65, RANKL, RANK proteins, up-regulating OPG protein, and inhibiting systemic inflammation.

摘要

目的 探讨补肾通络方(BSTL)对胶原诱导性关节炎(CIA)大鼠骨破坏的治疗作用及其对NF-κB/RANK/RANKL通路的抑制作用。方法 将SD大鼠随机分为空白对照组、CIA模型组、甲氨蝶呤(MTX,1 mg/kg)组、BSTL 0.5 g/kg组和BSTL 2 g/kg组,每组10只。除对照组外,其余大鼠于尾根部皮下注射Ⅱ型胶原(Col2)建立CIA模型。连续给予MTX或BSTL方剂28天后,采用HE染色观察关节组织病理变化。免疫组织化学法检测滑膜组织中NF-κB p65表达。ELISA法分析细胞因子及抗Col2水平。Western blotting法检测RANKL、RANK和骨保护素(OPG)蛋白表达。结果 与CIA模型组比较,BSTL 2 g/kg组大鼠连续给药28天后足爪体积、关节炎指数(AI)、血清IL-1β、IL-18、TNF-α、抗Col2-IgG、抗Col2-IgG2a、RANK和RANKL水平降低,血清OPG水平升高。此外,Western blotting结果显示,BSTL 2 g/kg组NF-κB p65、RANK和RANKL蛋白表达降低,OPG蛋白表达升高。结论 BSTL可通过下调NF-κB p65、RANKL、RANK蛋白表达,上调OPG蛋白表达,抑制全身炎症反应,从而减轻类风湿性关节炎。

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