Effect of Modified Erchentang on Bronchioles of Rats with Chronic Obstructive Pulmonary Disease by HMGB1/RAGE/NF-<italic style="font-style: italic">κ</italic>B Signaling Pathway

SHANG Lizhi; LI Yaoyang; JI Shu; XIE Wenying; SHANG Haofan; CHEN Zhuang; LIU Gaoyang; WANG Qi

doi:10.13422/j.cnki.syfjx.20230101

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Effect of Modified Erchentang on Bronchioles of Rats with Chronic Obstructive Pulmonary Disease by HMGB1/RAGE/NF-κB Signaling Pathway

更新时间：2023-02-15

- Effect of Modified Erchentang on Bronchioles of Rats with Chronic Obstructive Pulmonary Disease by HMGB1/RAGE/NF-κB Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 6, Pages: 44-54(2023)
- 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.20230101
  CLC： R2-0;R22;R285.5;R289;R33
- Published：20 March 2023，
  
  Published Online：30 November 2022，
  
  Received：09 August 2022，
- 稿件说明：
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尚立芝,李耀洋,季书等.二陈汤加味通过HMGB1/RAGE/NF-κB信号通路对COPD大鼠细支气管炎症的影响[J].中国实验方剂学杂志,2023,29(06):44-54.

SHANG Lizhi,LI Yaoyang,JI Shu,et al.Effect of Modified Erchentang on Bronchioles of Rats with Chronic Obstructive Pulmonary Disease by HMGB1/RAGE/NF-κB Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(06):44-54.
尚立芝,李耀洋,季书等.二陈汤加味通过HMGB1/RAGE/NF-κB信号通路对COPD大鼠细支气管炎症的影响[J].中国实验方剂学杂志,2023,29(06):44-54. DOI： 10.13422/j.cnki.syfjx.20230101.

SHANG Lizhi,LI Yaoyang,JI Shu,et al.Effect of Modified Erchentang on Bronchioles of Rats with Chronic Obstructive Pulmonary Disease by HMGB1/RAGE/NF-κB Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(06):44-54. DOI： 10.13422/j.cnki.syfjx.20230101.

摘要

目的

观测二陈汤加味对慢性阻塞性肺疾病（COPD）大鼠细支气管中高迁移率族蛋白1（HMGB1）/晚期糖基化终产物受体（RAGE）/核转录因子-

B（NF-

B）通路中关键分子表达的影响，探讨二陈汤加味通过HMGB1/RAGE/NF-

B信号通路对COPD细支气管炎症的作用及分子机制。

方法

60只SD大鼠随机分为6组：正常组、模型组、二陈汤加味低、中、高剂量组（5、10、20 g·kg

-1

）和丙酮酸乙酯（EP）组（HMGB1抑制剂），每组10只。以烟熏联合气管滴注脂多糖的方法制备COPD大鼠模型。二陈汤加味各干预组灌胃（

）给药，并腹腔注射林格溶液4 mL；EP组

等体积生理盐水，并腹腔注射EP（0.04 g·kg

-1

）；正常组和模型组等体积生理盐水

、并等体积林格溶液腹腔注射，连续干预21 d。酶联免疫吸附测定法检测支气管肺泡灌洗液（BALF）中HMGB1、趋化因子CXCL1和CXCL2、单核细胞趋化因子-1（MCP-1）的含量；实时荧光定量聚合酶链式反应（Real-time PCR）检测肺组织中HMGB1、RAGE和NF-

B p65 mRNA表达，免疫组化（IHC）检测细支气管组织中HMGB1、RAGE、磷酸化（p）-

B p65和

-平滑肌肌动蛋白（

-SMA）蛋白表达。

结果

与正常组比较，模型组用力肺活量（FVC）、第1秒末时间肺活量（FEV1）和FEV1/FVC均显著降低（

0.01）；BALF中HMGB1、CXCL1、CXCL2和MCP-1的含量均显著升高（

0.01）；肺组织HMGB1、RAGE、NF-

B p65 mRNA表达显著增加（

0.01）；HMGB1、RAGE、p-NF-

B p65和

-SMA蛋白表达明显增强（

0.05，

0.01）。与模型组比较，二陈汤加味中、高剂量组FEV1/FVC均明显提高（

0.05，

0.01）；BALF中HMGB1、CXCL1、CXCL2和MCP-1含量均明显降低（

0.05，

0.01）；HMGB1、RAGE、NF-

B p65 mRNA表达明显减少（

0.05，

0.01）；HMGB1、RAGE、p-NF-

B p65和

-SMA蛋白表达均明显减弱（

0.05，

0.01）。

结论

二陈汤加味能有效对抗COPD细支气管炎症反应。其机制可能与通过下调HMGB1、RAGE mRNA表达，抑制NF-

B活化，减少HMGB1、CXCL1、CXCL2和MCP-1的释放，从而抑制细支气管炎症损伤及异常修复有关。

Abstract

Objective

To study the effect of modified Erchentang on the expression of key molecules in the high mobility group Box 1 protein （HMGB1）/receptor for advanced glycation endproduct （RAGE）/nuclear factor-

B （NF-

B） signaling pathway in bronchioles of rats with chronic obstructive pulmonary disease （COPD）， to explore the mechanism of modified Erchentang against bronchiolar inflammation of COPD rats via HMGB1/RAGE/NF-

B signaling pathway.

Method

Sixty SD rats were randomly divided into normal group， model group， modified Erchentang low-， medium- and high-dose groups （5， 10， 20 g·kg

-1

·d

-1

） and ethyl pyruvate （HMGB1 inhibitor） group， with 10 in each group. The COPD rat model was prepared by cigarette smoke combined with tracheal injection of lipopolysaccharide （LPS）. After modeling， the modified Erchentang groups were given corresponding drugs （

） and Ringer's solution （4 mL，

）， while the EP group was treated with equal volume of normal saline （

） and EP （0.04 g·kg

-1

·d

-1

，

）. The normal group and the model group received equal volume of normal saline （

） and Ringer's solution （

） for 21 consecutive days. The contents of HMGB1， chemokine （C-X-C motif） ligand 1 （CXCL1）， CXCL2 and monocyte chemotactic protein-1 （MCP-1） in bronchoalveolar lavage fluid （BALF） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expressions of HMGB1， RAGE and NF-

B p65 were determined by Real-time polymerase chain reaction （Real-time PCR）， and the protein expressions of HMGB1， RAGE， p-NF-

B p65， and alpha-smooth muscle actin （

-SMA） in bronchioles tissue of rats were determined by immunohistochemistry （IHC）.

Result

Compared with the conditions in the normal group， the forced vital capacity （FVC）， forced expiratory volume in the first second （FEV1） and FEV1/FVC in the model group were decreased （

0.01） while the contents of HMGB1， CXCL1， CXCL2 and MCP-1 in BALF were increased （

0.01）. And the model group presented higher mRNA expressions of HMGB1， RAGE and NF-

B p65 （

0.01） and protein expressions of HMGB1， RAGE， p-NF-

B p65 and

-SMA （

0.05，

0.01） than the normal group. Compared with the model group， the modified Erchentang medium- and high-dose groups had increased FEV1/FVC （

0.05，

0.01）， lowered contents of HMGB1， CXCL1， CXCL2 and MCP-1 in BALF （

0.05，

0.05）， and reduced mRNA expressions of HMGB1， RAGE and NF-

B p65 （

0.05，

0.01） and protein expressions of HMGB1， RAGE， p-NF-

B p65 and

-SMA （

0.05，

0.01）.

Conclusion

Modified Erchentang can resist bronchiolar inflammation of COPD rats. The mechanism may be related to down-regulating the mRNA expressiona of HMGB1 and RAGE， inhibiting the activity of NF-

κB

， and reducing the release of HMGB1， CXCL1， CXCL2 and MCP-1， thus suppressing the inflammatory injury and abnormal repair of bronchioles.

关键词

慢性阻塞性肺疾病二陈汤高迁移率族蛋白1（HMGB1）晚期糖基化终产物受体（RAGE）核转录因子-κB（NF-κB）

Keywords

chronic obstructive pulmonary disease （COPD）Erchentanghigh mobility group Box 1 protein （HMGB1）receptor for advanced glycation endproduct （RAGE）nuclear factor-κB （NF-κB）

references

钟南山.慢性阻塞性肺疾病在中国［J］.中国实用内科杂志，2011，31（5）：321-323.

CHRISTENSON S A，SMITH B M，BAFADHEL M，et al.Chronic obstructive pulmonary disease［J］.Lancet，2022，399（10342）：2227-2242.

CHEN L，SUN X，ZHONG X.Role of RAGE and its ligand HMGB1 in the development of COPD［J］.Postgrad Med，2022，134（8）：763-775.

ZHANG P，XIN X，FANG L，et al.HMGB1 mediates aspergillus fumigatus induced inflammatory response in alveolar macrophages of COPD mice via activating MyD88/NF-κB and syk/PI3K signalings［J］.Int Immunopharmacol，2017，53（32）：125-132.

ZHANG M，LU Y，LIU L，et al.Role and mechanism of miR-181a-5p in mice with chronic obstructive pulmonary disease by regulating HMGB1 and the NF-κB pathway［J］.Cells Tissues Organs，2022，doi：10.1159/000522155http://dx.doi.org/10.1159/000522155.

WONG S L，TO J，SANTOS J，et al．Proteomic analysis of extracellular HMGB1 identifies binding partners and exposes its potential role in airway epithelial cell homeostasis［J］.J Proteome Res，2018，17（1）：33-45.

CHANG J H，LEE Y L，LAIMAN V，et al.Air pollution-regulated E-cadherin mediates contact inhibition of proliferation via the hippo signaling pathways in emphysema［J］.Chem Biol Interact， 2022，doi：10.1016/j.cbi.2021.109763http://dx.doi.org/10.1016/j.cbi.2021.109763.

POUWELS S D，HESSE L，WU X，et al.LL-37 and HMGB1 induce alveolar damage and reduce lung tissue regeneration via RAGE［J］.Am J Physiol Lung Cell Mol Physiol，2021，321（4）：L641-L652.

包永生，谢文英，王俊月.二陈汤研究进展［J］.中国实验方剂学杂，2019，25（23）：9-18.

尚立芝，吴珂，谢文英，等．二陈汤对慢性支气管炎气道黏液高分泌的影响［J］.中国老年学杂志，2018，38（8）：1922-1924．

尚立芝，季书，石龙涛，等.基于CXCL8-CXCR1/2轴探讨二陈汤加味对COPD大鼠的抗炎机制［J］．中国实验方剂学杂志，2020，26（11）：40-48．

徐莉莉，尚立芝，王博宇，等.二陈汤加味对慢性阻塞性肺病大鼠细支气管IL-19，IL-20R1，IL-20R2表达的影响［J］.中国实验方剂学杂志，2019，25（23）：41-46．

毛梦迪，尚立芝，徐莉莉，等.二陈汤加味对慢阻肺大鼠Th1/2/9细胞相关淋巴因子及IL-4R1/IL-13RA1的调节作用［J］.中国实验方剂学杂志，2020，26（20）：16-24．

邓楠，杨光伟，李小刚.丙酮酸乙酯对脑出血大鼠血清肿瘤坏死因子α和白介素6水平的影响［J］.实用心脑肺血管病杂志，2015，23（2）：49-52.

宋小莲，王昌惠，白冲．脂多糖结合熏烟法和单纯熏烟法建立慢性阻塞性肺病大鼠模型的比较［J］.第二军医大学学报，2010，31（3）：246-249．

SHU J，LU W，YANG K，et al．Establishment and evaluation of chronic obstructive pulmonary disease model by chronic exposure to motor vehicle exhaust combined with lipopolysaccharide instillation［J］.Exp Physiol，2018，103（11）：1532-1542．

慢性阻塞性肺疾病中医证候诊断标准（2011版）［J］.中医杂志，2012，53（2）：177-178.

何雯青，冯贞贞，春柳，等.慢性阻塞性肺疾病急性加重期证候疗效评价要素研究——基于文献研究结合专家咨询［J］.中医杂志，2022，63（5）：481-487.

尚立芝，季书，李耀洋，等.二陈汤加味对急性加重期COPD患者CXCL8及CXCR1/2蛋白表达的影响［J］.中国实验方剂学杂志，2019，25（24）：1-8.

尚立芝，季书，谢文英，等.二陈汤加味对COPD急性期患者CC16，SP-D及HAT/HDAC的影响［J］.中国实验方剂学杂志，2017，23（10）：163-170.

陈四清，谢文英，尚立芝，等.二陈汤加味对慢性阻塞性肺疾病急性加重期老年患者免疫功能及CCL18，CC16，IL-8和sICAM-1的影响［J］.中国实验方剂学杂志，2017，23（10）：171-177.

顾丹，朱兰.上海市徐汇区全科医师及居民慢性阻塞性肺疾病认知程度调查［J］.中国医学工程，2015，23（11）：64-65.

瞿波，周维，毛兵.慢性阻塞性肺疾病稳定期中医证型与肺功能的关系探讨［J］.华西医学，2015，30（10）：1853-1856.

BUSTIN M.Regulation of DNA-dependent activities by the functional motifs of the high-mobility-group chromosomal proteins［J］.Mol Cell Biol，1999，19（8）：5237-5246.

VIZOSO-VÁZQUEZ A，BARREIRO-ALONSO A，GONZÁLEZ-SISO M I，et al.HMGB proteins involved in TOR signaling as general regulators of cell growth by controlling ribosome biogenesis［J］.Curr Genet，2018，64（6）：1205-1213.

CHEN Q，YIN Y X，WEI J，et al.Increased expression of high mobility group box 1 （HMGB1） in the cytoplasm of placental syncytiotrophoblast from preeclamptic placentae［J］.Cytokine，2016，85：30-36.

HAYAKAWA K，ARAI K，LO E H.Role of ERK map kinase and CRM1 in IL-1beta-stimulated release of HMGB1 from cortical astrocytes［J］.Glia，2010，58（8）：1007-1015.

LUO Y，CHIHARA Y，FUJIMOTO K，et al.High mobility group box 1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy［J］.Eur J Cancer，2013，49（3）：741-751.

TODOROVA J，PASHEVA E.High mobility group B1 protein interacts with its receptor RAGE in tumor cells but not in normal tissues［J］.Oncol Lett，2012，3（1）：214-218.

ALLAM V，FAIZ A，LAM M，et al.RAGE and TLR4 differentially regulate airway hyperresponsiveness： Implications for COPD［J］.Allergy，2021，76（4）：1123-1135.

JEONG J，LEE J，LIM J，et al.Soluble RAGE attenuates AngⅡ-induced endothelial hyperpermeability by disrupting HMGB1-mediated crosstalk between AT1R and RAGE［J］.Exp Mol Med，2019，51（9）：1-15.

SHI Y，ZHANG L，TENG J，et al.HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy［J］.Mol Med Rep，2018，17（4）：5125-5131.

YANG Y L，LIU M，CHENG X，et al.Myricitrin blocks activation of NF-κB and MAPK signaling pathways to protect nigrostriatum neuron in LPS-stimulated mice［J］.J Neuroimmunol，2019，337：577049.

MALIK P，HOIDAL J R，MUKHERJEE T K.Implication of RAGE polymorphic variants in COPD complication and anti-COPD therapeutic potential of sRAGE［J］.COPD，2021，18（6）：737-748.

KAMO N，KE B，GHAFFARI A A，et al．The ASC /Caspase-1/IL-1β signaling triggers inflammatory responses by promoting HMGB1 induction in liver ischemia-reperfusion injury［J］.Hepatology，2013，58（1）：351-362．

BHAT S M，MASSEY N，KARRIKER L A，et al.Ethyl pyruvate reduces organic dust-induced airway inflammation by targeting HMGB1-RAGE signaling［J］.Respir Res，2019，20（1）：27.

HOU C，KONG J，LIANG Y，et al.HMGB1 contributes to allergen-induced airway remodeling in a murine model of chronic asthma by modulating airway inflammation and activating lung fibroblasts［J］.Cell Mol Immunol，2015，12（4）：409-423.

PAN K，LU J，SONG Y.Artesunate ameliorates cigarette smoke-induced airway remodelling via PPAR-γ/TGF-β1/Smad2/3 signalling pathway［J］.Respir Res，2021，22（1）：91.

ZABINI D，CRNKOVIC S，XU H，et al.High-mobility group box-1 induces vascular remodelling processes via c-Jun activation［J］.J Cell Mol Med，2015，19（5）：1151-1161.

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Effect of Modified Erchentang on Bronchioles of Rats with Chronic Obstructive Pulmonary Disease by HMGB1/RAGE/NF-κB Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20230101

摘要

Abstract

关键词

Keywords

references