Effect of <italic style="font-style: italic">Dingchuan Granule </italic>（定喘颗粒） on Lung Tissue Oxidative Stress and Nrf2/Keap1/HO-1/NQO1 Pathway in Respiratory Syncytial Virus Pneumonia Model Rats

ZHANG Lai; ZHANG Xiuying; WEI Chenhao; ZHANG Shiyao; LI Zhaoyang; WANG Rui; ZHAO Hangyu

doi:10.13288/j.11-2166/r.2025.15.013

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Effect of Dingchuan Granule （定喘颗粒） on Lung Tissue Oxidative Stress and Nrf2/Keap1/HO-1/NQO1 Pathway in Respiratory Syncytial Virus Pneumonia Model Rats

更新时间：2025-07-31

- Effect of Dingchuan Granule （定喘颗粒） on Lung Tissue Oxidative Stress and Nrf2/Keap1/HO-1/NQO1 Pathway in Respiratory Syncytial Virus Pneumonia Model Rats
- Journal of Traditional Chinese Medicine Vol. 66, Issue 15, Pages: 1588-1596(2025)
- 作者机构：
  
  1.辽宁中医药大学第一临床学院，辽宁省沈阳市皇姑区崇山东路79号，116600
  2.辽宁中医药大学第一附属医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2025.15.013
  CLC：
- Received：09 March 2025，
  
  Revised：2025-05-27，
  
  Published：02 August 2025
- 稿件说明：
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张来,张秀英,魏晨浩等.定喘颗粒对呼吸道合胞病毒肺炎模型大鼠肺组织氧化应激及Nrf2/Keap1/HO-1/NQO1信号通路的影响[J].中医杂志,2025,66(15):1588-1596.

ZHANG Lai,ZHANG Xiuying,WEI Chenhao,et al.Effect of Dingchuan Granule （定喘颗粒） on Lung Tissue Oxidative Stress and Nrf2/Keap1/HO-1/NQO1 Pathway in Respiratory Syncytial Virus Pneumonia Model Rats[J].Journal of Traditional Chinese Medicine,2025,66(15):1588-1596.
张来,张秀英,魏晨浩等.定喘颗粒对呼吸道合胞病毒肺炎模型大鼠肺组织氧化应激及Nrf2/Keap1/HO-1/NQO1信号通路的影响[J].中医杂志,2025,66(15):1588-1596. DOI： 10.13288/j.11-2166/r.2025.15.013.

ZHANG Lai,ZHANG Xiuying,WEI Chenhao,et al.Effect of Dingchuan Granule （定喘颗粒） on Lung Tissue Oxidative Stress and Nrf2/Keap1/HO-1/NQO1 Pathway in Respiratory Syncytial Virus Pneumonia Model Rats[J].Journal of Traditional Chinese Medicine,2025,66(15):1588-1596. DOI： 10.13288/j.11-2166/r.2025.15.013.

摘要

目的

探讨定喘颗粒治疗呼吸道合胞病毒（RSV）肺炎的可能作用机制。

方法

将60只雄性SD大鼠随机分为对照组、模型组、利巴韦林组和定喘颗粒低、中、高剂量组，每组10只。除对照组外，其余各组大鼠进行呼吸道合胞病毒滴鼻建立RSV肺炎模型。造模成功后定喘颗粒低、中、高剂量组分别给予定喘颗粒3.47、6.93、13.86 g/（kg·d）灌胃，利巴韦林组给予利巴韦林颗粒15.75 mg/（kg·d）灌胃，各组均每天灌胃1次，连续灌胃1周；对照组、模型组大鼠仅做抓取给药动作。于末次给药24 h后，采用HE染色法观察肺组织病理变化并进行病理评分，比色法检测血清肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）、白细胞介素6（IL-6）炎症因子水平，Western Blot法检测肺组织核因子相关因子2（Nrf2）

、

Kelch样ECH相关蛋白1（Keap1）、血红素加氧酶1（HO-1）

、

NAD（P）H醌脱氢酶1（NQO1）蛋白水平，qRT-PCR法检测肺组织RSV载量、

Nrf2、Keap1、HO

1、NQO1

基因表达水平，化学荧光法检测

大鼠肺组织活性氧（ROS）水平，微量法检测大鼠肺组织谷胱甘肽（GSH）、丙二醛（MDA）水平。

结果

与对照组比较，其余各组大鼠肺组织病理评分、RSV载量、ROS、MDA水平及血清TNF-α、IL-1β、IL-6水平均明显升高，GSH水平降低，肺组织Keap1蛋白及其mRNA表达水平升高，Nrf2、HO-1、NQO1蛋白及其mRNA表达水平明显降低（

＜0.05）。与模型组比较，定喘颗粒低、中、高剂量组及利巴韦林组上述各指标均有不同程度改善（

＜0.05）。定喘颗粒各剂量组大鼠血清TNF-α、IL-1β、IL-6水平呈剂量依赖性，以定喘颗粒高剂量效果最佳（

＜0.05）。定喘颗粒高剂量组在降低肺组织ROS、MDA水平和升高GSH水平方面优于定喘颗粒低、中剂量组（

＜0.05）。定喘颗粒高剂量组和利巴韦林组在降低RSV载量方面优于定喘颗粒中剂量组（

＜0.05）。定喘颗粒高剂量组在改善Nrf2、Keap1、HO-1、NQO1蛋白水平方面优于利巴韦林组（

＜0.05）。

结论

定喘颗粒可能通过调控Nrf2/Keap1/HO-1/NQO1信号通路，抑制氧化应激，达到改善肺部炎症、治疗RSV肺炎的作用，且以高剂量效果最好。

Abstract

Objective

To explore the potential mechanism of

Dingchuan Granule

（定喘颗粒， DG） in the treatment of respiratory syncytial virus （RSV） pneumonia.

Methods

A total of 60 male Sprague Dawley （SD） rats were randomly divided into control group， model group， ribavirin group， DG low-dose group， DG middle-dose group， and DG high-dose group， with 10 rats in each group. Except for the control group， rats were administrated with RSV via intranasal drip. After model establishment， the DG low-， middle-， and high-dose groups were administrated via oral gavage with DG at 3.47， 6.93， and 13.86 g/（kg·d） respectively， while the ribavirin group was administrated via oral gavage with ribavirin at 15.75 mg/（kg·d）. The drug was given once daily for one week. The rats in the control group and the model group were not given any drug， only subjected to the grasping action. Twenty-four hours after the last administration， the pathological changes of lung tissues were observed and scored using HE staining. The levels of serum inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）， were detected by colorimetry. The protein levels of nuclear factor （erythroid derived 2）-like 2

（Nrf2）， Kelch-like ECH-associated protein 1 （Keap1）， heme oxygenase 1 （HO-1）， and NAD（P）H quinone dehydrogenase 1 （NQO1） in lung tissues were measured by Western Blot. The RSV load as well as the gene expression levels of

Nrf2

，

Keap1

，

， and

NQO1

in lung tissues were determined by qRT-PCR. The level of reactive oxygen species （ROS） in rat lung tissues was detected using chemiluminescence. The levels of glutathione （GSH） and malondialdehyde （MDA） in rat lung tissues were measured by a microassay.

Results

Compared with the control group， other groups had significant increases in pathological score of lung tissue， RSV load， levels of ROS， MDA， serum TNF-α， IL-1β， and IL-6； decrease in GSH level， increases in expression level of Keap1 protein and its mRNA in lung tissue， and significant decrease in levels of Nrf2， HO-1， expression level of NQO1 protein and its mRNA （

＜0.05）. Compared with the model group， all the above-mentioned indicators in the DG low-， middle-， and high-dose groups and the ribavirin group were improved to varying degree （

＜0.05）. The levels of serum TNF-α， IL-1β， and IL-6 in rats of DG dose groups showed a dose-dependent pattern， the DG high-dose group exhibiting the best effect （

＜0.05）. The DG high-dose group was superior to the DG low- and middle-dose groups in reducing the levels of ROS and MDA， and increasing the level of GSH in lung tissues （

＜0.05）. The DG high-dose group and the ribavirin group had better effect than the DG middle-dose group in reducing the RSV load （

＜0.05）. The DG high-dose group was superior to the ribavirin group in improving the protein levels of Nrf2， Keap1， HO-1， and NQO1 （

＜0.05）.

Conclusion

DG could inhibit oxidative stress by regulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway to improve pulmonary inflammation and treat RSV pneumonia， with the DG high-dose group showing the best effect.

关键词

Keywords

references

AGAC A ， KOLBE SM ， LUDLOW M ， et al . Host responses to respiratory syncytial virus infection ［J］. Viruses ， 2023 ， 15 （ 10 ）： 1999 .

ZHANG XL ， ZHANG X ， HUA W ， et al . Expert consensus on the diagnosis， treatment， and prevention of respiratory syncytial virus infections in children ［J］. World J Pediatr ， 2024 ， 20 （ 1 ）： 11 - 25 .

SIMÕES EAF ， DEVINCENZO JP ， BOECKH M ， et al . Challenges and opportunities in developing respiratory syncytial virus therapeutics ［J］. J Infect Dis ， 2015 ， 211 （ suppl 1 ）： S1 - S20 .

SIMÕES EAF ， BONT L ， MANZONI P ， et al . Past， present and future approaches to the prevention and treatment of respiratory syncytial virus infection in children ［J］. Infect Dis Ther ， 2018 ， 7 （ 1 ）： 87 - 120 .

胥会英，韩新民 . 肺炎喘嗽病因病机古今认识差异探讨［J］. 实用中医药杂志， 2008 ， 24 （ 12 ）： 803 - 804 .

高媛媛，王雪峰，张秀英，等 . 小儿定喘颗粒治疗儿童病毒性肺炎（痰热闭肺证）的临床研究［J］. 中国中西医结合儿科学， 2023 ， 15 （ 4 ）： 351 - 355 .

KOMARAVELLI N ， ANSAR M ， GAROFALO RP ， et al . Respiratory syncytial virus induces NRF2 degradation through a promyelocytic leukemia protein-ring finger protein 4 dependent pathway ［J］. Free Radic Biol Med ， 2017 ， 113 ： 494 - 504 . doi： 10.1016/j.freeradbiomed. 2017.10.380 http://dx.doi.org/10.1016/j.freeradbiomed.2017.10.380 .

SAMIMI F ， BAAZM M ， NADI Z ， et al . Evaluation of antioxidant effects of coenzyme Q10 against hyperglycemia-mediated oxidative stress by focusing on Nrf2/Keap1/HO-1 signaling pathway in the liver of diabetic rats ［J］. Iran J Med Sci ， 2024 ， 49 （ 10 ）： 661 - 670 .

SCHMIDT ME ， OOMENS AGP ， VARGA SM . Vaccination with a single-cycle respiratory syncytial virus is immunogenic and protective in mice ［J］. J Immunol ， 2019 ， 202 （ 11 ）： 3234 - 3245 .

KULKARNI HS ， LEE JS ， BASTARACHE JA ， et al . Update on the features and measurements of experimental acute lung injury in animals： an official American Thoracic Society workshop report ［J］. Am J Respir Cell Mol Biol ， 2022 ， 66 （ 2 ）： e1 - e14 .

徐叔云，卞如濂，陈修 . 药理实验方法学［M］. 北京：人民卫生出版社， 2003 ： 202 - 203 .

BELPERIO JA ， KEANE MP ， BURDICK MD ， et al . Critical role for CXCR2 and CXCR2 ligands during the pathogenesis of ventilator-induced lung injury ［J］. J Clin Invest ， 2002 ， 110 （ 11 ）： 1703 - 1716 .

周涛，张秀英，王雪峰，等 . 定喘颗粒对呼吸道合胞病毒肺炎幼鼠肺组织病毒载量及气道阻力的影响［J］. 中国中西医结合儿科学， 2014 ， 16 （ 1 ）： 26 - 30，93 .

TYLUTKA A ， WALAS Ł ， ZEMBRON-LACNY A . Level of IL-6， TNF， and IL-1β and age-related diseases： a systematic review and meta-analysis ［J］. Front Immunol ， 2024 ， 15 ： 1330386 . doi： 10.3389/fimmu.2024. 1330386 http://dx.doi.org/10.3389/fimmu.2024.1330386 .

李天萍，黄霞飞，杨蕉，等 . 呼吸道合胞病毒感染性肺炎患儿的TNF-α和IL-1β水平及TLR4信号通路作用初步探究［J］. 中华医院感染学杂志， 2020 ， 30 （ 6 ）： 919 - 922 .

KALER J ， HUSSAIN A ， PATEL K ， et al . Respiratory syncytial virus： a comprehensive review of transmission， pathophysiology， and manifestation ［J］. Cureus ， 2023 ， 15 （ 3 ）： e36342 .

HOSAKOTE YM ， LIU T ， CASTRO SM ， et al . Respiratory syncytial virus induces oxidative stress by modulating antioxidant enzymes ［J］. Am J Respir Cell Mol Biol ， 2009 ， 41 （ 3 ）： 348 - 357 .

JOMOVA K ， RAPTOVA R ， ALOMAR SY ， et al . Reactive oxygen species， toxicity， oxidative stress， and antioxidants： chronic diseases and aging ［J］. Arch Toxicol ， 2023 ， 97 （ 10 ）： 2499 - 2574 .

GAROFALO RP ， KOLLI D ， CASOLA A . Respiratory syncytial virus infection： mechanisms of redox control and novel therapeutic opportunities ［J］. Antioxid redox signal ， 2013 ， 18 （ 2 ）： 186 - 217 .

SUN YY ， ZHU HJ ， ZHAO RY ， et al . Remote ischemic conditioning attenuates oxidative stress and inflammation via the Nrf2/HO-1 pathway in MCAO mice ［J］. Redox biol ， 2023 ， 66 ： 102852 . doi： 10.1016/j.redox.2023. 102852 http://dx.doi.org/10.1016/j.redox.2023.102852 .

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Effect of Dingchuan Granule （定喘颗粒） on Lung Tissue Oxidative Stress and Nrf2/Keap1/HO-1/NQO1 Pathway in Respiratory Syncytial Virus Pneumonia Model Rats

DOI：10.13288/j.11-2166/r.2025.15.013

摘要

Abstract

关键词

Keywords

references