Effects of Metformin and Montelukast in Acute and Chronic Allergic Asthma Mouse Models

GUO Yan-rong; YAN Yan

doi:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0606

您当前的位置：

首页 >

文章列表页 >

Effects of Metformin and Montelukast in Acute and Chronic Allergic Asthma Mouse Models

Basic Research | 更新时间：2024-02-19

- Effects of Metformin and Montelukast in Acute and Chronic Allergic Asthma Mouse Models
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 43, Issue 6, Pages: 905-915(2022)
- 作者机构：
  
  广东省生物医学影像重点实验室//中山大学附属第五医院分子影像中心，广东珠海 519000
- 作者简介：
  
  YAN Yan； E-mail： yanyan35@mail.sysu.edu.cn
- 基金信息：
- DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0606
  CLC： R392.8
- Received：30 June 2022，
  
  Published：20 November 2022
- 稿件说明：
移动端阅览
郭妍蓉,严彦.二甲双胍和孟鲁司特在急性和慢性过敏性哮喘小鼠模型中的作用[J].中山大学学报（医学科学版）,2022,43(06):905-915.

GUO Yan-rong,YAN Yan.Effects of Metformin and Montelukast in Acute and Chronic Allergic Asthma Mouse Models[J].Journal of Sun Yat-sen University(Medical Sciences),2022,43(06):905-915.
郭妍蓉,严彦.二甲双胍和孟鲁司特在急性和慢性过敏性哮喘小鼠模型中的作用[J].中山大学学报（医学科学版）,2022,43(06):905-915. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0606.

GUO Yan-rong,YAN Yan.Effects of Metformin and Montelukast in Acute and Chronic Allergic Asthma Mouse Models[J].Journal of Sun Yat-sen University(Medical Sciences),2022,43(06):905-915. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0606.

摘要

目的

对比分析屋尘螨（HDM）诱导的过敏性哮喘小鼠模型26 d的急性模型和59 d的慢性模型，评价二甲双胍和孟鲁司特对气道炎症和气道重塑病理效应的改善作用。

方法

HDM致敏和激发构建急性和慢性过敏性哮喘小鼠模型，设置药物干预组包括阳性药物对照组（HDM+布地奈德）、二甲双胍组（HDM+二甲双胍）和孟鲁司特钠组（HDM+孟鲁司特钠），干预药物于每次HDM激发前1 h或30 min，经滴鼻（布地奈德1mg/kg）或腹腔注射（二甲双胍200 mg/kg、孟鲁司特钠10 mg/kg）给药。各实验组小鼠处死后苏木素-伊红染色和马松染色分析小鼠的肺部病理特征；采用Image J软件进行气道炎症细胞浸润评分和胶原沉积评分，以及分析支气管形态参数，包括支气管壁厚度和支气管平滑肌厚度；采用ELISA方法检测小鼠血清总IgE水平，qRT-PCR检测炎症因子

IL-4

、

IL-5

、

IL-13

mRNA转录水平。

结果

慢性模型小鼠的血清总IgE水平、气道周围胶原沉积程度、气道平滑肌厚度显著高于急性模型小鼠（

＜0.05）。布地奈德干预可以显著改善急性组小鼠的气道炎症（

＜0.05）；和HDM造模组相比，二甲双胍干预对HDM诱导急性哮喘小鼠有明显的气道炎症改善（

＜0.05）作用，对气道重塑无显著作用（

＞0.05），对慢性模型小鼠的气道炎症和气道重塑均无显著作用（

＞0.05）；在慢性组的孟鲁司特钠干预组中，小鼠的气道炎症和气道重塑均无明显的改善（

＞0.05）。

结论

相比26 d的急性模型，59 d的慢性哮喘模型有更高水平的炎症反应和气道重塑效应，二甲双胍能有效改善HDM诱导急性哮喘小鼠中的气道炎症，孟鲁司特钠对慢性哮喘小鼠气道炎症和气道重塑均无显著作用。

Abstract

Objective

To compare the effects of metformin and montelukast on airway inflammation and remodeling in the acute and chronic house dust mite （HDM）-induced asthma mouse models.

Methods

HDM-induced acute and chronic asthma mouse models were established and treated with 1mg/kg of budesonide， 200 mg/kg of metformin， or 10 mg/kg of montelukast， respectively. The drugs were administrated via intranasal instillation or intraperitoneal injection 1 h or 30 min prior to each HDM challenge. Hematoxylin-Eosin and Masson’s trichrome staining were used to analyze the lungpathological characteristics of mice. The score analysis of airway inflammatory cell infiltration and collagen deposition and the measurement of bronchial morphological parameters including bronchial wall thickness and bronchial smooth muscle thickness were determined by Image J software. Total serum IgE level， mRNA transcription level of inflammatory factors

IL-4

，

IL-5

， and

IL-13

were detected by ELISA and qRT-PCR.

Results

HDM-induced chronic model had significantly increased total serum IgE level， airway collagen deposition and thickness of airway smooth muscle than the acute model （

0.05）. Budesonide significantly attenuated airway inflammation in the HDM-induced acute model （

0.05）. Metformin significantly improved airway inflammation （

0.05） and had no significant effect on airway remodeling （

0.05） in the HDM-induced acute model. Both metformin and montelukast had no significant effect on airway inflammation and remodeling （

0.05） in the chronic model.

Conclusion

Compared with the 26-day acute model， the 59-day chronic asthma mouse model has a higher level of serum IgE， pulmonary Th2 cytokine transcripts and airway collagen deposition. Metformin can effectively ameliorate airway inflammation in the HDM-induced acute mouse model， and montelukast has no significant effect on airway inflammation and remodeling in the HDM-induced chronic mouse model.

关键词

Keywords

references

Huang K ， Yang T ， Xu J ， et al . Prevalence， risk factors， and management of asthma in China： a national cross-sectional study ［J］. Lancet （London， England）， 2019 ， 394 （ 10196 ）： 407 - 418 .

Olivieri M ， Zock JP ， Accordini S ， et al . Risk factors for new-onset cat sensitization among adults： a population-based international cohort study ［J］. J Allergy Clin Immunol ， 2012 ， 129 （ 2 ）： 420 - 425 .

Permaul P ， Hoffman E ， Fu C ， et al . Allergens in urban schools and homes of children with asthma ［J］. Pediatr Allergy Immunol ， 2012 ， 23 （ 6 ）： 543 - 549 .

McCracken JL ， Veeranki SP ， Ameredes BT ， et al . Diagnosis and management of asthma in adults： a review ［J］. JAMA ， 2017 ， 318 （ 3 ）： 279 - 290 .

Nials AT ， Uddin S . Mouse models of allergic asthma： acute and chronic allergen challenge ［J］. Dis Model Mech ， 2008 ， 1 （ 4-5 ）： 213 - 220 .

Gregory LG ， Lloyd CM . Orchestrating house dust mite-associated allergy in the lung ［J］. Trends Immunol ， 2011 ， 32 （ 9 ）： 402 - 411 .

Kuruvilla ME ， Lee FE ， Lee GB . Understanding asthma phenotypes， endotypes， and mechanisms of disease ［J］. Clin Rev Allergy Immunol ， 2019 ， 56 （ 2 ）： 219 - 233 .

Tan YY ， Zhou HQ ， Lin YJ ， et al . FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells ［J］. Mil Med Res ， 2022 ， 9 （ 1 ）： 7 .

Guo Y ， Shi J ， Wang Q ， et al . Metformin alleviates allergic airway inflammation and increases Treg cells in obese asthma ［J］. J Cell Mol Med ， 2021 ， 25 （ 4 ）： 2279 - 2284 .

Davino-Chiovatto JE ， Oliveira-Junior MC ， MacKenzie B ， et al . Montelukast， leukotriene inhibitor， reduces LPS-Induced acute lung inflammation and human neutrophil activation ［J］. Arch Bronconeumol （Engl Ed）， 2019 ， 55 （ 11 ）： 573 - 580 .

WHO . Global Asthma Report 2019 ［EB/OL］. （ 2021-05-11 ）［ 2022-06-15 ］. https：//www.who.int/news-room/fact-sheets/detail/asthma https://www.who.int/news-room/fact-sheets/detail/asthma .

Bunyavanich S ， Schadt EE . Systems biology of asthma and allergic diseases： a multiscale approach ［J］. J Allergy Clin Immunol ， 2015 ， 135 （ 1 ）： 31 - 42 .

Fahy JV . Type 2 inflammation in asthma--present in most， absent in many ［J］. Nat Rev Immunol ， 2015 ， 15 （ 1 ）： 57 - 65 .

Rangarajan S ， Bone NB ， Zmijewska AA ， et al . Metformin reverses established lung fibrosis in a bleomycin model ［J］. Nat Medi ， 2018 ， 24 （ 8 ）： 1121 - 1127 .

Bharath LP ， Agrawal M ， McCambridge G ， et al . Metformin enhances autophagy and normalizes mitochondrial function to alleviate aging-associated inflammation ［J］. Cell Metab ， 2020 ， 32 （ 1 ）： 44 - 55 .

Xue J ， Li X ， Liu P ， et al . Inulin and metformin ameliorate polycystic ovary syndrome via anti-inflammation and modulating gut microbiota in mice ［J］. Endocr J ， 2019 ， 66 （ 10 ）： 859 - 870 .

Glockler-Lauf SD ， Finkelstein Y ， Zhu J ， et al . Montelukast and neuropsychiatric events in children with asthma： a nested case-control study ［J］. J Pediatr ， 2019 ， 209 ： 176 - 182.e4 .

Malmström K ， Pelkonen AS ， Mäkelä MJ . Remodeling， inflammation and airway responsiveness in early childhood asthma ［J］. Curr Opin Allergy Clin Immunol ， 2013 ， 13 （ 2 ）： 203 - 210 .

Views

620

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Metformin Facilitates Intracellular Amyloid β Degradation by Increasing Insulin-degrading Enzyme Expression in M146L Cell Line

Effects of Short-term High-salt Diet on Airway Inflammation in Mice with Allergic Asthma

Measurements of Airway Dimensions of Multi-slice Spiral CT in Patients with COPD: Relationship with Lung Function

Metformin Improves Insulin Sensitivity of Rat Model with Polycystic Ovary Syndrome and Its Mechanism

Endobronchial Ultrasound Detecting Airway Remodeling in Chronic Obstructive Pulmonary Disease

Related Author

XU Cai-li

TANG Jiao-ling

GUO Kai-hua

XIE Ting

CHEN Yan-qiu

YANG Yan

ZOU Jin-chao

TIAN Ze-zhong

Related Institution

Department of Anatomy and Physiology， Zhongshan School of Medicine， Sun Yat-Sen University

School of Public Health， Sun Yat-sen University

Guangdong Provincial Key Laboratory of Food， Nutrition and Health， School of Public Health， Sun Yat-sen University（Guangzhou Campus）

Guangdong Engineering Technology Research Center of Nutrition Translation

School of Public Health （Shenzhen）， Sun Yat-sen University

Postal code：510080
Tel：020-87690764，87690974，87690694 Email：xbmed@mail.sysu.edu.cn
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19 京公网安备11010802024621
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