风湿宁对风寒湿痹证CIA大鼠模型滑膜组织中TLR4/NF-B信号通路的影响

董小君; 王永辉; 侯渊; 张晨曦; 赵乐; 周然

doi:10.13422/j.cnki.syfjx.20181033

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风湿宁对风寒湿痹证CIA大鼠模型滑膜组织中TLR4/NF-B信号通路的影响

药理 | 更新时间：2024-01-04

- 风湿宁对风寒湿痹证CIA大鼠模型滑膜组织中TLR4/NF-B信号通路的影响
- Effect of Fengshining on TLR4/NF-B Signal Pathway in Synovial Tissue of Wind-Cold-Dampness Arthralgia Syndrome CIA Rat Model
- 中国实验方剂学杂志 2018年24卷第10期页码：123-129
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金面上项目（81473589）
- DOI：10.13422/j.cnki.syfjx.20181033
  中图分类号： R-332;R285.5
- 纸质出版日期：2018
- 稿件说明：
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董小君, 王永辉, 侯渊, 等. 风湿宁对风寒湿痹证CIA大鼠模型滑膜组织中TLR4/NF-B信号通路的影响[J]. 中国实验方剂学杂志, 2018,24(10):123-129.

DONG Xiao-jun, WANG Yong-hui, HOU Yuan, et al. Effect of Fengshining on TLR4/NF-B Signal Pathway in Synovial Tissue of Wind-Cold-Dampness Arthralgia Syndrome CIA Rat Model[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(10): 123-129.
董小君, 王永辉, 侯渊, 等. 风湿宁对风寒湿痹证CIA大鼠模型滑膜组织中TLR4/NF-B信号通路的影响[J]. 中国实验方剂学杂志, 2018,24(10):123-129. DOI： 10.13422/j.cnki.syfjx.20181033.

DONG Xiao-jun, WANG Yong-hui, HOU Yuan, et al. Effect of Fengshining on TLR4/NF-B Signal Pathway in Synovial Tissue of Wind-Cold-Dampness Arthralgia Syndrome CIA Rat Model[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(10): 123-129. DOI： 10.13422/j.cnki.syfjx.20181033.

摘要

目的：探讨风湿宁对风寒湿痹证胶原诱导性关节炎（CIA）大鼠模型滑膜组织中Toll样受体4/核转录因子-κB（TLR4/NF-κB）信号通路的影响及相关的作用机制。方法：SPF级雌性Wistar大鼠随机分为6组，分别为正常组，模型组，阳性药组（来氟米特片，2.33 mg·kg-1），风湿宁低、中、高剂量组（9.12，18.24，36.48 g·kg-1），每组9只。除正常组外，其余各组大鼠采用风寒湿外感致病因素刺激，结合牛Ⅱ型胶原乳化剂诱导的方法，制备风寒湿痹证CIA大鼠模型。造模成功后，各组大鼠给予相应药物灌胃干预，每日1次，连续4周。观察药物对大鼠关节肿胀度，酶联免疫吸附测定法（ELISA）血清类风湿因子（RF），环瓜氨酶肽（ACPA），白细胞介素（IL）-1β，IL-10，肿瘤坏死因子-α（TNF-α）含量，实时荧光定量聚合酶链式反应（Real-time PCR）及蛋白免疫印迹法（Western blot）滑膜组织中TLR4，髓样分化因子88（MyD88），NF-κB酶抑制蛋白α（IκBα），NF-κB mRNA和蛋白表达的情况。结果：与正常组比较，模型组CIA大鼠模型的关节肿胀度明显升高，血清RF，ACPA，IL-1β，TNF-α含量显著升高，IL-10含量显著降低，滑膜组织中TLR4，MyD88，IκBα，NF-κB mRNA和蛋白表达显著升高（P<0.05，P<0.01）；与模型组比较，风湿宁低、中、高剂量组可明显降低风寒湿痹证CIA大鼠模型的关节肿胀度与血清RF，ACPA，IL-1β，TNF-α含量，升高血清IL-10水平，下调滑膜组织中TLR4，MyD88，IκB-α，NF-κB mRNA与蛋白表达量（P<0.05，P<0.01）。结论：风湿宁可能通过抑制TLR4/NF-κB信号通路，从而抑制IL-1β，TNF-α的产生，起到治疗RA的作用，且其疗效与药物剂量有一定相关性。

Abstract

Objective: To investigate the effect and mechanism of Fengshining on wind-cold-dampness arthralgia syndrome CIA rat model in synovial tissue based on Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signal pathway. Method: SPF female Wistar rats were randomly divided into six groups:the blank control group

the model control group

the positive control group (2.33 mg·kg-1)

the low

medium and high-dose Fengshining groups (9.12

18.24

36.48 g·kg-1)

with nine rats in each group. Except for the blank control group

the rest rats were included into the wind-cold-dampness arthralgia syndrome CIA rat model through the wind-cold-dampness stimulation combing with bovine type Ⅱ collagen. Each group of rats was given the corresponding drug by gavage once a day for four weeks after the successful modeling. Joint swelling degree of the rats was observed. Serum rheumatoid factors (RF)

anti-cyclic citrullinated peptide antibodies (ACPA)

interleukin-1β (IL-1β)

interleukin-10 (IL-10)

tumour necrosis factor-α (TNF-α)were detected. TLR4

myeloid differentiation factor88 (MyD88)

IκBα

NF-κB mRNA and protein expressions in synovial tissue were measured. Result: Compared with the blank control group

the wind-cold-dampness arthralgia syndrome CIA model group showed significant increase in joint swelling degree and serum RF

ACPA

IL-1β

TNF-α content

and significant reduction in IL-10 content. The mRNA and protein expressions of TLR4

MyD88

IκB-α

NF-κB in synovial tissue were significantly increased (P<0.05

P<0.01). Compared with the model group

low

medium and high-dose Fengshining groups showed significant decrease in joint swelling degree and serum RF

ACPA

IL-1β

TNF-α content in the wind-cold-dampness arthralgia syndrome CIA rat model

increase in serum IL-10 level

and down-regulation in mRNA and protein expressions of TLR4

MyD88

IκBα

NF-κB (P<0.05

P<0.01). Conclusion: Fengshining may play a role in the treatment of RA by inhibiting TLR4/NF-κB signal pathway and the production of IL-1β and TNF-α. Its efficacy is correlated with drug dose to some extent.

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