Mechanism of Flemiphilippinin D Regulating Inflammatory Response in CIA Rats Through TLR2/MyD88/NF-<italic style="font-style: italic">κ</italic>B Signaling Pathway

QIN Qingxia; HE Lianhua; WEI Mei; HE Huan; MA Liuhui; PANG Ting; ZHOU Lan

doi:10.13422/j.cnki.syfjx.20230840

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Mechanism of Flemiphilippinin D Regulating Inflammatory Response in CIA Rats Through TLR2/MyD88/NF-κB Signaling Pathway

更新时间：2023-08-07

- Mechanism of Flemiphilippinin D Regulating Inflammatory Response in CIA Rats Through TLR2/MyD88/NF-κB Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 17, Pages: 134-141(2023)
- 作者机构：
  
  1.广西农业职业技术大学食品药品工程学院，南宁 530007
  2.广州中医药大学第四临床医学院，广东深圳 518033
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230840
  CLC： R2-0;R33;R289;R684.3
- Published：05 September 2023，
  
  Published Online：29 June 2023，
  
  Received：04 May 2023，
- 稿件说明：
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覃清霞,何莲花,魏梅等.蔓性千斤拔素D通过TLR2/MyD88/NF-κB信号通路调控CIA大鼠炎症反应的相关机制[J].中国实验方剂学杂志,2023,29(17):134-141.

QIN Qingxia,HE Lianhua,WEI Mei,et al.Mechanism of Flemiphilippinin D Regulating Inflammatory Response in CIA Rats Through TLR2/MyD88/NF-κB Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(17):134-141.
覃清霞,何莲花,魏梅等.蔓性千斤拔素D通过TLR2/MyD88/NF-κB信号通路调控CIA大鼠炎症反应的相关机制[J].中国实验方剂学杂志,2023,29(17):134-141. DOI： 10.13422/j.cnki.syfjx.20230840.

QIN Qingxia,HE Lianhua,WEI Mei,et al.Mechanism of Flemiphilippinin D Regulating Inflammatory Response in CIA Rats Through TLR2/MyD88/NF-κB Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(17):134-141. DOI： 10.13422/j.cnki.syfjx.20230840.

摘要

目的

观察蔓性千斤拔素D对大鼠胶原诱导型关节炎（CIA）的作用并探讨其作用机制。

方法

将40只大鼠随机分为正常组、CIA组、甲氨蝶呤（MTX）组（1.35 mg·kg

-1

）、蔓性千斤拔素D低剂量组（1.5 mg·kg

-1

）及蔓性千斤拔素D高剂量组（3.0 mg·kg

-1

），每组8只，除正常组外，其余均采用Ⅱ型胶原诱导CIA模型。给药组通过灌胃给予相应药液，正常组给予相应体积生理盐水，MTX组每周1次，蔓性千斤拔素D各组每天1次，共给药28 d。实验中记录各组大鼠关节炎评分和关节肿胀度，苏木素-伊红（HE）染色观察各组大鼠踝关节病理学变化，酶联免疫吸附测定法（ELISA）检测大鼠血清炎症因子白细胞介素（IL）-1

、IL-6、IL-8、肿瘤坏死因子（TNF）-

水平，实时荧光定量聚合酶链式反应（Real-time PCR）检测Toll样受体2（TLR2）、髓样分化因子88（MyD88）、核转录因子-

B（NF-

B） p65 mRNA的表达量，蛋白免疫印迹法（Western blot）检测TLR2、MyD88、NF-

B p65蛋白的表达量。

结果

与正常组比较，CIA组大鼠踝关节明显肿胀，关节炎临床评分及关节肿胀度显著升高（

0.01），踝关节组织结构明显破坏，血清炎性因子IL-1

、IL-6、IL-8、TNF-

含量显著升高（

0.01），TLR2、MyD88、NF-

B p65 mRNA及蛋白表达水平显著升高（

0.01）。与CIA组比较，各给药组大鼠关节炎临床评分及关节肿胀度均明显降低（

0.05，

0.01），踝关节组织结构病理变化明显改善，血清IL-1

、IL-6、IL-8、TNF-

含量均明显降低（

0.05，

0.01），踝关节TLR2、MyD88、NF-

B p65 mRNA及蛋白表达水平均明显下降（

0.05，

0.01）。

结论

蔓性千斤拔素D在一定程度上可降低类风湿关节炎大鼠炎性因子的表达，能起到良好的治疗作用，其作用机制可能是通过抑制TLR2/MyD88/NF-

B信号通路的活化而发挥抗炎作用。

Abstract

Objective

To observe the effect of Flemiphilippinin D on collagen-induced arthritis （CIA） in rats and explore its mechanism.

Method

Forty rats were randomly divided into normal group， CIA group， methotrexate （MTX） group （1.35 mg·kg

-1

）， low-dose Flemiphilippinin D group （1.5 mg·kg

-1

）， and high-dose Flemiphilippinin D group （3.0 mg·kg

-1

）， with eight rats in each group. Except for the normal group， the CIA model was induced by type Ⅱ collagen. Each group was given corresponding liquid medicine or normal saline， once a week in the MTX group， and once a day in the Flemiphilippinin D groups for a total of 28 days. The arthritis score and joint swelling degree of rats were experimentally recorded. Pathological changes in the ankle joint of rats were observed by hematoxylin-eosin （HE） staining. Serum levels of inflammatory cytokines interleukin （IL）-1

， IL-6， IL-8， and tumor necrosis factor （TNF）-

were detected by enzyme-linked immunoabsorbent assay （ELISA）， and the mRNA expression of Toll-like receptor 2 （TLR2）， myeloid differentiation factor 88 （MyD88）， and nuclear transcription factor-

B （NF-

B） p65 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of TLR2， MyD88， and NF-

B p65 were detected by Western blot.

Result

Compared with the normal group， the ankle joint of the CIA group was significantly swollen， and the clinical score of arthritis and the degree of joint swelling were significantly increased （

0.01）. The ankle joint tissue structure was significantly damaged， and the levels of inflammatory factors IL-1

， IL-6， IL-8， and TNF-

in serum were significantly increased （

0.01）. The mRNA levels and protein levels of TLR2， MyD88， and NF-

B p65 were significantly increased（

0.01）. Compared with the CIA group， arthritis clinical score and joint swelling of rats in each administration group were significantly reduced （

0.05，

0.01）， and the pathological changes in the ankle joint were significantly improved. The contents of serum IL-1

， IL-6， IL-8， and TNF-

were significantly decreased （

0.05，

0.01）. The mRNA levels and protein levels of TLR2， MyD88， and NF-

B p65 in the ankle joint were significantly decreased （

0.05，

0.01）.

Conclusion

To a certain extent， Flemiphilippinin D can reduce the expression of inflammatory factors in rheumatoid arthritis rats and play a good therapeutic effect. It works perhaps by inhibiting the activation of the TLR2/MyD88/NF-

B signaling pathway and thus shows an anti-inflammatory effect.

关键词

蔓性千斤拔素D类风湿关节炎Toll样受体2（TLR2）髓样分化因子88（MyD88）核转录因子-κB（NF-κB）

Keywords

Flemiphilippinin Drheumatoid arthritisToll-like receptor 2 （TLR2）myeloid differentiation factor 88 （MyD88）nuclear transcription factor-κB （NF-κB）

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Mechanism of Flemiphilippinin D Regulating Inflammatory Response in CIA Rats Through TLR2/MyD88/NF-κB Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20230840

摘要

Abstract

关键词

Keywords

references