主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2020, Vol. 43 ›› Issue (4): 289-295.doi: 10.3969/j.issn.1006-2157.2020.04.005

• 中药药理 • 上一篇    下一篇

补肾祛寒治尪汤对胶原诱导关节炎大鼠抗炎与抗骨破坏的作用及对Wnt/β-catenin通路的影响

徐愿1,阎小萍1,肖诚1,马茹2,陈光耀2,陶庆文1#   

  1. 1 中日友好医院中医风湿病科 免疫炎性疾病北京市重点实验室 北京 100029;
    2 北京中医药大学
  • 收稿日期:2020-01-03 出版日期:2020-04-30 发布日期:2020-05-14
  • 通讯作者: 陶庆文,男,主任医师,博士生导师,研究方向:中医药治疗风湿病,E-mail:taoqg1@sina.com
  • 作者简介:徐愿,男,博士,副主任医师
  • 基金资助:
    国家自然科学基金青年科学基金项目(No. 81603588)

Effects of kidney-supplementing cold-dispelling Zhi Wang Tang decoction on inflammation, bone erosion and Wnt/β-catenin pathway in rats with collagen-induced arthritis*

Xu Yuan1, Yan Xiaoping1, Xiao Cheng1, Ma Ru2, Chen Guangyao2, Tao Qingwen1#   

  1. 1 TCM Department of Rheumatism, Beijing Key Lab of Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing 100029. China;
    2 Beijing University of Chinese Medicine, Beijing 100029, China
  • Received:2020-01-03 Online:2020-04-30 Published:2020-05-14
  • Contact: Tao Qingwen, Chief Physician.Department of TCM Rheumatism & Beijing Key Laboratory of Autoimmune and Inflammatory Diseases,China-Japan Friendship Hospital, No.2 Yinghua DongJie, Chaoyang District,Beijing 100029. E-mail: taoqgl@sina.com
  • Supported by:
    National Natural Science Foundation of China (No.81603588)

摘要: 目的 研究补肾祛寒治尪汤改善胶原诱导关节炎(CIA)大鼠炎症和骨破坏的作用及可能机制。方法 大鼠分为空白组,模型组,补肾祛寒治尪汤组(25 g/kg灌胃,每天1次),甲氨蝶呤组(3 mg/kg灌胃,3天1次)。除空白组外,其余大鼠分别于饲养1、2周时尾部注射0.1 mL胶原乳剂(含牛Ⅱ型胶原200 μg)制备关节炎模型。给药时间为初次免疫1周后开始,连续给药6周,每周记录关节炎指数(AI)。实验第7周处死动物,采集膝关节行HE染色,用免疫组化、免疫印迹法和荧光定量法评估肿瘤坏死因子α(TNF-α)、基质金属蛋白酶13(MMP13)、β-链蛋白(β-catenin)的表达。结果 治疗6周后,补肾祛寒治尪汤组AI评分低于模型组(P<0.05);HE染色显示,补肾祛寒治尪汤组骨破坏较模型组明显减轻。与模型组比较,补肾祛寒治尪汤组TNF-α、MMP13、β-catenin蛋白及mRNA的表达减少(P<0.05)。结论 补肾祛寒治尪汤能改善CIA大鼠骨破坏与关节炎症状,作用机制可能与调节Wnt/β-catenin通路,抑制TNF-α、MMP13表达有关。

关键词: 类风湿关节炎, 胶原诱导关节炎, 补肾祛寒治尪汤, Wnt/β-catenin通路, 大鼠

Abstract: Objective To investigatethe effects of kidney-supplementing cold-dispelling Zhi Wang Tang(ZWT)decoction on relieving inflammation and bone erosion and modulating TNF-α, MMP13, β-catenin in rats of collagen-induced arthritis(CIA) models. Methods SD rats were injected at the tails with emulsion (0.1 mL) containing bovine type Ⅱ collagen (200 μg) after 1-2 weeks of orientation feeding to simulate the development of arthritis except those in the blank group.Rats were divided into the following four groups: blank group (n=6),model group(n=7), ZWT group (25 g/kg, oral, once a day, n=7), MTX group (methotrexate, 3 mg/kg, oral, once every three days, n=7).Intervention was administered for 6 continuous weeks starting in the week after immunization. Arthritis indexes (AI) were recorded.All rats were then sacrificed at week 7.Knee joint samples were taken for HE staining. Levels of TNF-a, MMP13 and β-catenin were evaluated with immunohistochemistry, Western blot and qPCR assays. Results At week 6 of intervention, AI scores in the ZWT group were lower than those of model group (P<0.05); HE staining result indicated that bone erosion changes in the ZWT group were also significantly relieved compared to the model group. Expressions of β-catenin, pro-inflammatory cytokines TNF-α and MMP13 were all reduced (P<0.05) compared to the model group. Conclusion ZWT seemed to relieve inflammation and bone erosion in CIA rats;its mechanism maybe associated with modulating Wnt/β-catenin pathway, and inhibiting the expression TNF-α and MMP13.

Key words: rheumatoid arthritis, collagen-induced arthritis, Zhi Wang decoction, Wnt/β-catenin pathway, rats

中图分类号: 

  • R285.5