Effect of PM2.5 on the Airway Remodeling in Chronic Obstructive Pulmonary Disease Model Rats and the Protective Effect of the<italic style="font-style: italic"> Effective</italic>-<italic style="font-style: italic">component Compatibility of Bufei Yishen Formula （</italic>补肺益肾组分方<italic style="font-style: italic">）</italic>

Jing WANG; Ya LI; Jiansheng LI; Peng ZHAO; Yange TIAN; Xuefang LIU; Huihui HE; Rui JIA; Caili ZHANG

doi:10.13288/j.11-2166/r.2021.24.012

您当前的位置：

首页 >

文章列表页 >

Effect of PM2.5 on the Airway Remodeling in Chronic Obstructive Pulmonary Disease Model Rats and the Protective Effect of the Effective-component Compatibility of Bufei Yishen Formula （补肺益肾组分方）

更新时间：2021-12-17

- Effect of PM2.5 on the Airway Remodeling in Chronic Obstructive Pulmonary Disease Model Rats and the Protective Effect of the Effective-component Compatibility of Bufei Yishen Formula （补肺益肾组分方）
- Journal of Traditional Chinese Medicine Vol. 62, Issue 24, Pages: 2176-2183(2021)
- 作者机构：
  
  1.河南中医药大学呼吸疾病中医药防治省部共建协同创新中心，河南省郑州市郑东新区金水东路156号，450046
  2.河南中医药大学中医药科学院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2021.24.012
  CLC：
- Received：24 June 2021，
  
  Revised：2021-08-28，
  
  Published：17 December 2021
- 稿件说明：
移动端阅览
王晶,李亚,李建生等.PM2.5对慢性阻塞性肺疾病模型大鼠气道重塑的影响及补肺益肾组分方的保护作用[J].中医杂志,2021,62(24):2176-2183.

WANG Jing,LI Ya,LI Jiansheng,et al.Effect of PM2.5 on the Airway Remodeling in Chronic Obstructive Pulmonary Disease Model Rats and the Protective Effect of the Effective-component Compatibility of Bufei Yishen Formula （补肺益肾组分方）[J].Journal of Traditional Chinese Medicine,2021,62(24):2176-2183.
王晶,李亚,李建生等.PM2.5对慢性阻塞性肺疾病模型大鼠气道重塑的影响及补肺益肾组分方的保护作用[J].中医杂志,2021,62(24):2176-2183. DOI： 10.13288/j.11-2166/r.2021.24.012.

WANG Jing,LI Ya,LI Jiansheng,et al.Effect of PM2.5 on the Airway Remodeling in Chronic Obstructive Pulmonary Disease Model Rats and the Protective Effect of the Effective-component Compatibility of Bufei Yishen Formula （补肺益肾组分方）[J].Journal of Traditional Chinese Medicine,2021,62(24):2176-2183. DOI： 10.13288/j.11-2166/r.2021.24.012.

摘要

目的

观察PM2.5对慢性阻塞性肺疾病（COPD）模型大鼠气道重塑的影响及补肺益肾组分方的保护作用与可能机制。

方法

72只SD大鼠随机分为空白组、PM2.5组、COPD组、PM2.5+COPD组、补肺益肾组分方组和氨茶碱组，每组12只。第1~8周，除空白组和PM2.5组外，其余各组给予香烟熏吸联合反复细菌感染制备COPD大鼠模型。第9~16周，除空白组和COPD组外，其余各组给予大气实时浓缩PM2.5全身暴露；同时，补肺益肾组分方组和氨茶碱组分别给予补肺益肾组分方6.48 mg/（kg·d）和氨茶碱混悬液54 mg/（kg·d）灌胃，其余各组给予生理盐水灌胃（雌鼠1.5 ml/只、雄鼠2 ml/只）。PM2.5末次暴露24 h内取材，观察肺组织病理形态和超微结构；采用免疫组化法检测肺组织碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）、α平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原蛋白（COL Ⅰ），Ⅲ型胶原蛋白（COL Ⅲ）表达；采用ELISA法检测支气管-肺泡灌洗液中基质金属蛋白酶9（MMP-9）、基质金属蛋白酶12（MMP-12）和金属蛋白酶组织抑制因子1（TIMP-1）水平。

结果

与空白组比较，PM2.5组、COPD组和PM2.5+COPD组大鼠肺组织出现肺泡壁和支气管壁增厚、支气管狭窄、血管增生、炎症细胞浸润和Ⅱ型肺泡上皮结构破坏，且以PM2.5+COPD组尤为显著；与PM2.5+COPD组比较，补肺益肾组分方组和氨茶碱组以上肺组织病理损伤显著改善。与空白组比较，PM2.5组、COPD组和PM2.5+COPD组大鼠肺组织中bFGF、VEGF、α-SMA、COL Ⅰ、COL Ⅲ阳性表达，支气管-肺泡灌洗液中MMP-9和MMP-12均显著升高，TIMP-1显著降低（

＜0.05或

＜0.01）；与PM2.5组或COPD组比较，PM2.5+COPD组bFGF、VEGF、α-SMA、COL Ⅰ、COL Ⅲ和MMP-9、MMP-12显著升高，TIMP-1显著降低（

＜0.05或

＜0.01）；与PM2.5+COPD组比较，补肺益肾组分方组和氨茶碱组bFGF、VEGF、α-SMA、COL Ⅰ、MMP-9、MMP-12显著降低，TIMP-1显著升高，补肺益肾组分方组COL Ⅲ显著降低（

＜0.05或

＜0.01）。

结论

PM2.5暴露显著加重COPD模型大鼠气道重塑，补肺益肾组分方可以延缓PM2.5暴露环境下COPD气道重塑进程，其机制可能与抑制胶原沉积、改善蛋白酶/抗蛋白酶失衡等相关。

Abstract

Objective

To explore the effect of PM2.5 exposure on the airway remodeling of chronic obstructive pulmonary disease （COPD） model rats and the protective effect as well as the possible mechanism of the

effective

component compatibility of Bufei Yishen Formula

（补肺益肾组分方， ECC-BYF）.

Methods

A total of 72 SD rats were randomized into control group， PM2.5 group， COPD group， PM2.5+COPD group， ECC-BYF group， and aminophylline group， with 12 rats in each group. The COPD rat model was prepared in all groups except for the control group and PM2.5 group by using repeated cigarette smoke inhalation and bacterial infection during week 1 to 8； then rats in all groups except for the control group and COPD group were exposed to real-time atmospheric concentrated PM2.5 during week 9 to 16. Meanwhile， rats in the ECC-BYF group and aminophylline group were given ECC-BYF （6.48 mg/kg·d） and aminophylline （54 mg/kg·d） by gavage， respectively， while rats in other groups were given normal saline （1.5 ml for female rat， 2 ml for male rat） once daily from week 9 to 16. Animals were sacrificed within 24 hours of the last PM2.5 exposure. The histomorphological changes and ultrastructure of lung tissue were observed. The expression of basic fibroblast growth factor （bFGF）， vascular endothelial growth factor （VEGF）， α-smooth muscle actin （α-SMA）， collagen Ⅰ （COL Ⅰ） and collagen Ⅲ （COL Ⅲ） in lung tissues were detected by immunohistochemistry， and the levels of matrix metalloproteinases （MMP）-9， MMP-12， and metalloproteinase-inhibitor （TIMP）-1 in bronchoalveolar lavage fluid （BALF） were determined by enzyme-linked immunosorbent assay （ELISA）.

Results

Compared with the control group， lung tissues derived from rats in PM2.5 group， COPD group， and PM2.5+COPD group showed marked alveolar and bronchial wall thickness， airway narrowing， vascular hyperplasia， inflammatory cells infiltration， and disordered structure of type Ⅱ alveolar epithelium， and more severe changes were seen in PM2.5+COPD group； compared with the PM2.5+COPD group， more improvement on the above mentioned lung tissue outcomes were shown in the ECC-BYF group and aminophylline group. Compared with the control group， there were increased positive expressions of bFGF， VEGF， α-SMA and COL Ⅰ and COL Ⅲ， elevated MMP-9 and MMP-12 in BALF， as well as decreased TIMP-1 in the PM2.5 group， COPD group， and PM2.5+COPD group （

＜0.05 or

＜0.01）； compared with the PM2.5 group or the COPD group， there were increased bFGF， VEGF， α-SMA， COL Ⅰ， COL Ⅲ and MMP-9， MMP-12， and decreased TIMP-1 （

＜0.05 or

＜0.01） PM2.5+COPD group； compared with the PM2.5+COPD group， the ECC-BYF group and aminophylline group have significantly decreased bFGF， VEGF， α-SMA， COL I， MMP-9， MMP-12， increased TIMP-1， and lowered COL Ⅲ （

＜0.05 or

＜0.01）.

Conclusion

PM2.5 exposure markedly aggravates the airway remodeling in rats with preexisting COPD， while ECC-BYF could alleviate the airway remodeling progression of COPD rats caused by PM2.5 exposure； the mechanism may be related to the inhibition of collagen deposition， and the improvement of protease/anti-protease imbalance.

关键词

Keywords

references

Global Initiative for Chronic Obstructive Lung Disease . Global strategy for the diagnosis ， management， and prevention of chronic obstructive pulmonary disease （2021 gold report）［EB/OL］. （ 2020-11-17 ）［ 2021-08-24 ］. https：//goldcopd.org/2021-gold-reports/ https://goldcopd.org/2021-gold-reports/ .

FALCON-RODRIGUEZ CI ， OSORNIO-VARGAS AR ， SADA-OVALLE I ， et al . Aeroparticles， composition， and lung diseases ［J］. Front Immunol ， 2016 ， 7 ： 3 . doi： 10. 3389/fimmu.2016.00003 http://dx.doi.org/10.3389/fimmu.2016.00003 .

SALVI S . Tobacco smoking and environmental risk factors for chronic obstructive pulmonary disease ［J］. Clin Chest Med ， 2014 ， 35 （ 1 ）： 17 - 27 .

LI MH ， FAN LC ， MAO B ， et al . Short-term exposure to ambient fine particulate matter increases hospitalizations and mortality in COPD： a systematic review and meta-analysis ［J］. Chest ， 2016 ， 149 （ 2 ）： 447 - 458 .

LI SY ， LI JS ， WANG MH ， et al . Effects of comprehensive therapy based on traditional Chinese medicine patterns in stable chronic obstructive pulmonary disease： a four center， open-label， randomized， controlled study ［J］. BMC Complement Altern Med ， 2012 ， 12 ： 197 . doi： 10.1186/1472-6882-12-197 http://dx.doi.org/10.1186/1472-6882-12-197 .

LI JS ， LI SY ， XIE Y ， et al . The effective evaluation on symptoms and quality of life of chronic obstructive pulmonary disease patients treated by comprehensive therapy based on traditional Chinese medicine patterns ［J］. Complement Ther Med ， 2013 ， 21 （ 6 ）： 595 - 602 .

LI JS ， LI Y ， LI SY ， et al . Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation responses in rats with stable chronic obstructive pulmonary disease ［J］. J Chin Integrat Med ， 2012 ， 10 （ 9 ）： 1039 - 1048 .

ZHAO P ， LI JS ， YANG LP ， et al . Integration of transcriptomics， proteomics， metabolomics and systems pharmacology data to reveal the therapeutic mechanism underlying Chinese herbal Bufei Yishen formula for the treatment of chronic obstructive pulmonary disease ［J］. Mol Med Rep ， 2018 ， 17 （ 4 ）： 5247 - 5257 .

王晶，李亚，李建生，等．调补肺肾系列方药对PM2.5致肺损伤大鼠炎症和氧化应激的影响［J］．中医杂志， 2019 ， 60 （ 5 ）： 415 - 421 ．

LI JS ， LIU XF ， DONG HR ， et al . Effective-constituent compatibility-based analysis of Bufei Yishen formula， a traditional herbal compound as an effective treatment for chronic obstructive pulmonary disease ［J］. J Integr Med ， 2020 ， 18 （ 4 ）： 351 - 362 .

LI JS ， MA JD ， TIAN YG ， et al . Effective-component compatibility of Bufei Yishen formula Ⅱ inhibits mucus hypersecretion of chronic obstructive pulmonary disease rats by regulating EGFR/PI3K/ mTOR signaling ［J］. J Ethnopharmacol ， 2020 ， 257 ： 112796 . doi： 10.1016/j.jep.2020.112796 http://dx.doi.org/10.1016/j.jep.2020.112796 .

LI JS ， XIE Y ， ZHAO P ， et al . A chinese herbal formula ameliorates COPD by inhibiting the inflammatory response via downregulation of p65， JNK， and p38 ［J］. Phytomedicine ， 2021 ， 83 ： 153475 . doi： 10.1016/j.phymed.2021.153475 http://dx.doi.org/10.1016/j.phymed.2021.153475 .

LI Y ， LI SY ， LI JS ， et al . A rat model for stable chronic obstructive pulmonary disease induced by cigarette smoke inhalation and repetitive bacterial infection ［J］. Biol Pharm Bull ， 2012 ， 35 （ 10 ）： 1752 - 1760 .

WANG J ， LI Y ， ZHAO P ， et al . Exposure to air pollution exacerbates inflammation in rats with preexisting COPD ［J］. Mediators Inflamm ， 2020 ： 4260204 . doi： 10.1155/2020/4260204 http://dx.doi.org/10.1155/2020/4260204 .

黄继汉，黄晓辉，陈志扬，等．药理试验中动物间和动物与人体间的等效剂量换算［J］．中国临床药理学与治疗学， 2004 ， 9 （ 9 ）： 1069 - 1072 ．

GBD 2017 Causes of Death Collaborators . Global， regional， and national age-sex-specific mortality for 282 causes of death in 195 countries and territories， 1980-2017： a systematic analysis for the global burden of disease study 2017 ［J］. Lancet ， 2018 ， 392 （ 10159 ）： 1736 - 1788 .

Institute for Health Metrics and Evaluation （IHME） . GBD Compare ［EB/OL］. （ 2020-10 ）［ 2021-08-24 ］. https：//vizhub.healthdata.org/gbd-compare/ https://vizhub.healthdata.org/gbd-compare/ .

ABBEY DE ， BURCHETTE RJ ， KNUTSEN SF ， et al . Long-term particulate and other air pollutants and lung function in nonsmokers ［J］. Am J Respir Crit Care Med ， 1998 ， 158 （ 1 ）： 289 - 298 .

AMARAL AFS ， PATEL J ， KATO BS ， et al . Airflow obstruction and use of solid fuels for cooking or heating： BOLD results ［J］. Am J Respir Crit Care Med ， 2018 ， 197 （ 5 ）： 595 - 610 .

SINT T ， DONOHUE JF ， GHIO AJ . Ambient air pollution particles and the acute exacerbation of chronic obstructive pulmonary disease ［J］. Inhal Toxicol ， 2008 ， 20 （ 1 ）： 25 - 29 .

HIROTA N ， MARTIN JG . Mechanisms of airway remodeling ［J］. Chest ， 2013 ， 144 （ 3 ）： 1026 - 1032 .

JONES RL ， NOBLE PB ， ELLIOT JG ， et al . Airway remodelling in COPD： It's not asthma ！［J］. Respirology ， 2016 ， 21 （ 8 ）： 1347 - 1356 .

BAKAKOS P ， PATENTALAKIS G ， PAPI A . Vascular biomarkers in asthma and COPD ［J］. Curr Top Med Chem ， 2016 ， 16 （ 14 ）： 1599 - 1609 .

PAVLISA G ， PAVLISA G ， KUSEC V ， et al . Serum levels of VEGF and bFGF in hypoxic patients with exacerbated COPD ［J］. Eur Cytokine Netw ， 2010 ， 21 （ 2 ）： 92 - 98 .

LÖFDAHL M ， KAARTEENAHO R ， LAPPI-BLANCO E ， et al . Tenascin-C and alpha-smooth muscle actin positive cells are increased in the large airways in patients with COPD ［J］. Respir Res ， 2011 ， 12 （ 1 ）： 48 .

CAZZOLA M ， CALZETTA L ， BARNES PJ ， et al . Efficacy and safety profile of xanthines in COPD： a network meta-analysis ［J］. Eur Respir Rev ， 2018 ， 27 （ 148 ）： 180010 .

GRZELA K ， LITWINIUK M ， ZAGORSKA W ， et al . Airway Remodeling in Chronic Obstructive Pulmonary Disease and Asthma： the Role of Matrix Metalloproteinase-9 ［J］. Arch Immunol Ther Exp （Warsz）， 2016 ， 64 （ 1 ）： 47 - 55 .

查看原文

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of Bufei Yishen Formula （补肺益肾方） on the Efferocytosis of Alveolar Macrophages and PPAR γ Pathway in Chronic Obstructive Pulmonary Disease Model Mice

Clinical Observation on Yiqi Bushen Huoxue Formula Combined with Salmeterol / Fluticasone Inhalation Powder in Treating 35 Cases of Stable Chronic Obstructive Pulmonary Disease

Effects of Electro-Acupuncture Based on the Midnight-Noon Ebb-Low Method with Hour-Prescription on BMAL1 Protein and NETs Markers in Lung Tissue of Chronic Obstructive Pulmonary Disease Model Rats with Lung-Qi Deficiency Syndrome

Discussion on the Role of Ferroptosis in Chronic Obstructive Pulmonary Disease from the Perspective of "Qi Deficiency with Retention and Stagnation"

Syndrome Differentiation and Treatment Patterns in Chronic Obstructive Pulmonary Disease Guided by the Theory of Lung Collateral Disease

Related Author

Yingshuo WU

Yiwan SHANG

Danhua MENG

Zhexu ZHOU

Xing CHEN

Yaosong WU

Shanshan REN

Yan LIU

Related Institution

Henan University of Chinese Medicine

The First Affiliated Hospital of Heilongjiang University of Chinese Medicine

Heilongjiang University of Chinese Medicine

School of Integrative Medicine， Anhui University of Chinese Medicine

Key Laboratory of Ministry of Education in Xin'an Medicine， Anhui University of Chinese Medicine

Address：No.16, Nanxiao street, Dongzhimen, Dongcheng District, Beijing Postal code：100700
Tel：010-64035632 Email：jtcmcn@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19 京公网安备11010102007558号
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

Effect of PM2.5 on the Airway Remodeling in Chronic Obstructive Pulmonary Disease Model Rats and the Protective Effect of the Effective-component Compatibility of Bufei Yishen Formula （补肺益肾组分方）

DOI：10.13288/j.11-2166/r.2021.24.012

摘要

Abstract

关键词

Keywords

references