Mechanism of Modified Erchentang on Signaling Pathway of TLR4/MyD88/NF-κB in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease

Li-zhi SHANG; Shu JI; Guo-qiang WANG; Xiao-hui CHEN; Wen-ying XIE; Yao-yang LI; Guang-yuan ZHANG; Long-tao SHI; Li-li XU

doi:10.13422/j.cnki.syfjx.20192203

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Mechanism of Modified Erchentang on Signaling Pathway of TLR4/MyD88/NF-κB in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease

Study on the Effect of Modified Erchentang on Chronic Obstructive Pulmonary Disease | 更新时间：2021-02-09

- Mechanism of Modified Erchentang on Signaling Pathway of TLR4/MyD88/NF-κB in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 23, Pages: 65-72(2019)
- 作者机构：
  
  河南中医药大学，郑州　 450046
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20192203
  CLC： R2-0; R22; R285.5; R289
- Received：20 May 2019，
  
  Published Online：09 August 2019，
  
  Published：05 December 2019
- 稿件说明：
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Li-zhi SHANG, Shu JI, Guo-qiang WANG, et al. Mechanism of Modified Erchentang on Signaling Pathway of TLR4/MyD88/NF-κB in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(23): 65-72.
DOI：

Li-zhi SHANG, Shu JI, Guo-qiang WANG, et al. Mechanism of Modified Erchentang on Signaling Pathway of TLR4/MyD88/NF-κB in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(23): 65-72. DOI： 10.13422/j.cnki.syfjx.20192203.

摘要

目的：

观察二陈汤加味对慢性阻塞性肺疾病(COPD)大鼠肺Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核转录因子-

B(NF-

B)通路及相关分子的影响，探讨二陈汤加味对COPD抗炎作用的分子机制。

方法：

将40只SD大鼠随机平均分为正常组、模型组、二陈汤加味组和EVP4593(NF-

B抑制剂)组。以香烟烟雾联合气管滴注脂多糖(LPS)方法制备COPD大鼠模型。二陈汤加味组以10 g·kg

－1

灌胃(

)，EVP4593组皮下注射1 mg·kg

－1

，正常组、模型组

等量生理盐水，连续干预14 d。酶联免疫吸附测定法(ELISA)检测血清高迁移率族蛋白B1(HMGB1)，趋化因子(CXCL)-2，CXCL-3和单核细胞趋化蛋白-1(MCP-1)水平，实时荧光定量聚合酶链式反应(Real-time PCR)，蛋白免疫印迹法(Western blot)分别检测肺匀浆中TLR4，MyD88，NF-

B p65 mRNA及蛋白表达水平，免疫组化(IHC)检测TLR4，MyD88，磷酸化NF-

B p65(p-NF-

B p65)在大鼠肺组织中的定位表达。

结果：

与正常组比较，模型组肺匀浆中TLR4，MyD88，NF-

B p65 mRNA及蛋白表达均显著增加(

0.01)，HMGB1，CXCL-2，CXCL-3和MCP-1含量显著升高(

0.01)。与模型组比较，二陈汤加味组TLR4，MyD88，NF-

B p65 mRNA及其蛋白表达均显著减弱(

0.05，

0.01)，HMGB1，CXCL-2，CXCL-3和MCP-1含量显著降低(

0.05，

0.01)。

结论：

二陈汤加味对COPD有抗炎作用，其机制可能与抑制TLR4/MyD88/NF-

B通路相关信号分子基因的表达，以及减少HMGB1，CXCL-2，CXCL-3和MCP-1的释放有关。

Abstract

Objective:

To study the effect of modified Erchentang on expressions of Toll-like receptor 4 (TLR4)

myeloid differentiation factor (MyD88) and nuclear factor-

B (NF-

B) genes in the lung tissue homogenate of rats with chronic obstructive pulmonary disease (COPD).

Method:

Forty SD rats were randomly divided into normal group

model group

modified Erchentang group and EVP4593 (NF-

B inhibitor) group. Rat COPD models were prepared through cigarette smoke and tracheal dripping with lipopolysaccharide (LPS). After the modeling

normal and model groups were intragastrically given normal saline solution

EVP4593 group was given EVP4593(1 mg·kg

-1

) through subcutaneous injection

and modified Erchentang group was given corresponding herbal drugs intragastrically (10 g·kg

-1

) for 14 days. The levels of high mobility group box 1(HMGB1)

chemokines CXCL-2

CXCL-3 and monocyte chemoattractant protein-1 (MCP-1) in rats serum were detected by enzyme-linked immunosorbent assay in rats serum. The expressions of Toll-like receptors 4(TLR4)

myeloid differentiation factor (MyD88) and nuclear factor-

B p65 (NF-

B p65) mRNA were detected by Real-time fluorescence quantitative PCR (Real-time PCR) method. Western blot were used to detect the levels of TLR4

MyD88

NF-

B p65 and p-NF-

B p65 protein. Immunohistochemistry (IHC) method was used to detect the localization and expressions of TLR4

MyD88 and p-NF-

B p65 protein in the lung tissue.

Result:

The mRNA and protein expressions of TLR4

MyD88 and NF-

B p65 were increased significantly (

0.01) in model group compared with normal group. The levels of HMGB1

CXCL-2

CXCL-3 and MCP-1 in the model group were significantly higher than those in the normal group (

0.01). Compared with model group

expressions of TLR4

MyD88 and NF-

B p65 mRNA and protein were decreased significantly (

0.05) in modified Erchentang.

Conclusion:

Modified Erchentang may inhibit the inflammatory response of COPD effectively. The mechanism may be related to the inhibition of the expressions of the signal molecule genes involved in the TLR4/MyD88/NF-

B pathway and the reduction of the release of HMGB1

CXCL-2

CXCL-3 and MCP-1.

关键词

Keywords

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