Effects of vitamin A combined with dexamethasone on airway epithelium structure and function in asthmatic mice

Jie HU; Wenjing ZOU; Yunting WANG; Zhou FU; Jihong DAI; Chao NIU

doi:10.16016/j.1000-5404.201906118

您当前的位置：

首页 >

文章列表页 >

Effects of vitamin A combined with dexamethasone on airway epithelium structure and function in asthmatic mice

Basic Medicine | 更新时间：2026-01-09

- Effects of vitamin A combined with dexamethasone on airway epithelium structure and function in asthmatic mice
- Journal of Third Military Medical University Vol. 41, Issue 22, Pages: 2158-2165(2019)
- 作者机构：
  
  1.400014 重庆，儿童发育疾病研究教育部重点实验室，儿童发育重大疾病国家国际科技合作基地，儿科学重庆市重点实验室
  2.400014 重庆，重庆医科大学附属儿童医院呼吸中心
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(81600022)
- DOI：10.16016/j.1000-5404.201906118
  CLC： R562.25;R677.11;R977.21
- Received：18 June 2019，
  
  Revised：2019-07-14，
  
  Published：30 November 2019
- 稿件说明：
移动端阅览
Jie HU, Wenjing ZOU, Yunting WANG, et al. Effects of vitamin A combined with dexamethasone on airway epithelium structure and function in asthmatic mice[J]. Journal of Third Military Medical University, 2019, 41(22): 2158-2165.
DOI：

Jie HU, Wenjing ZOU, Yunting WANG, et al. Effects of vitamin A combined with dexamethasone on airway epithelium structure and function in asthmatic mice[J]. Journal of Third Military Medical University, 2019, 41(22): 2158-2165. DOI： 10.16016/j.1000-5404.201906118.

摘要

目的

探讨维生素A联合糖皮质激素对哮喘小鼠气道上皮的结构和功能的影响。

方法

将6~8周SPF级C57bl/6雌性小鼠按随机数字表法分为5组:对照组、哮喘组(asthma)、地塞米松组(Dex)、维生素A组(VA)、地塞米松+维生素A组(D+VA)。asthma组、Dex组、VA组、D+VA组用屋尘螨建立哮喘模型，Dex组在最后3次激发前30 min，腹腔注射200 μL地塞米松溶液，VA组在建模第21天起给予维生素A特殊饲料，连续10 d，D+VA组的地塞米松和维生素A给予方法同Dex组和VA组，对照组用0.9%NaCl溶液代替，于末次激发24 h内行有创肺功能检测，测定小鼠气道高反应性(airway hyperresponsiveness，AHR)，留取支气管肺泡灌洗液(BALF)行细胞计数，行气管及左肺病理学检测，免疫组化染色检测肺组织E-cadherin的表达，Western blot检测肺组织caspase 3、cleaved caspase 3的表达。

结果

Dex组气管上皮损伤较asthma组加重，同时肺组织E-cadhein表达较asthma组降低(

0.05)，caspase 3及cl-caspase 3表达较asthma组升高(

0.01)。VA组AHR较asthma组降低(

0.05)，但BALF细胞计数、肺病理学检测结果与Dex组无明显差异。D+VA组AHR低于Dex组(

0.01)，且气道上皮损伤较Dex组明显减轻，同时肺组织E-cadherin表达较Dex组增加(

0.01)，caspase 3及cl-caspase 3表达较Dex组降低(

0.01)。

结论

地塞米松可以促进哮喘小鼠气道上皮凋亡，加重气道上皮的损伤，维生素A联合地塞米松应用哮喘小鼠时，可进一步降低哮喘小鼠的AHR，同时可以抑制气道上皮凋亡，减轻气道上皮的损伤。

Abstract

Objective

To observe the effects of vitamin A combined with glucocorticoid on the structure and function of airway epithelium in asthmatic mice.

Methods

Sixty specific pathogen-free female C57bl/6 mice (6 to 8 weeks old) were randomized equally into control group

asthma group

dexamethasone (Dex) group

vitamin A (VA) group

and dexamethasone plus vitamin A (D+VA) group. Except for those in the control group

all the mice were stimulated repeatedly with house dust mites to establish asthma models. At 30 min before the last 3 stimulations

the mice in Dex group were intraperitoneally injected with 200 μL of dexamethasone. The mice in VA group were given vitamin A-rich food for 10 consecutive days starting on 21 days after the modeling. The mice in D+VA group received both dexamethasone treatment and vitamin A feeding

and the control mice were injected with 0.9% NaCl only. Within 24 h after the last challenge

invasive lung function test was performed to assess airway hyperresponsiveness (AHR) of the mice

bronchoalveolar lavage fluid (BALF) was collected from the mice for cell counting

and the trachea and lungs were sampled for pathological examination with HE staining. The expression of E-cadherin

caspase 3 and cleaved caspase 3 in the lung tissue were detected using immunohistochemical staining and Western blotting.

Results

Dexamethasone treatment aggravated airway epithelial injury in the asthmatic mice and obviously lowered the expression of E-cadhein (

0.05) and increased the expression of caspase 3 and cleaved caspase 3 in the lung tissues(

0.01). The asthmatic mice receiving vitamin A treatment showed significantly lowered AHR(

0.05)

but their cell counts in the BALF and lung pathologies were similar with those in dexamethasone-treated mice. Compared with the mice with dexamethasone treatment

the mice receiving both dexamethasone and vitamin A treatment had significantly lowered AHR(

0.01)

lessened airway epithelial injury

lowered expression levels of caspase 3 and cleaved caspase 3(

0.01) and increased expression of E-cadherin in the lung tissues(

0.01).

Conclusion

Dexamethasone promotes apoptosis of airway epithelial cells in asthmatic mice to aggravate airway epithelial injury. Vitamin A combined with dexamethasone can better reduce AHR and inhibit airway epithelial cell apoptosis to maintain the structural and functional integrity of the airway epithelium in asthmatic mice.

关键词

Keywords

references

REDDEL H K, BATEMAN E D, BECKER A, et al . A summary of the new GINA strategy: a roadmap to asthma control[J ] . Eur Respir J, 2015, 46(3): 622-639. DOI: 10.1183/13993003.00853-2015.

刘传合, 洪建国, 尚云晓, 等.中国16城市儿童哮喘患病率20年对比研究[J].中国实用儿科杂志, 2015, 30(8): 596-600.

LIU C H, HONG J G, SHANG Y X, et al . Comparison of asthma prevalence in children from 16 cities of China in 20 years[J ] . Chin J Pract Pediatr, 2015, 30(8): 596-600.

RAMADAN A A, GAFFIN J M, ISRAEL E, et al . Asthma and corticosteroid responses in childhood and adult asthma[J ] . Clin Chest Med, 2019, 40(1): 163-177. DOI: 10.1016/j.ccm.2018.10.010.

HEKKING P P W, BEL E H. Developing and emerging clinical asthma phenotypes[J]. J Allergy Clin Immunol: Pract, 2014, 2(6): 671-680. DOI: 10.1016/j.jaip.2014.09.007.

GRAS D, CHANEZ P, VACHIER I, et al . Bronchial epithelium as a target for innovative treatments in asthma[J ] . Pharmacol Ther, 2013, 140(3): 290-305. DOI: 10.1016/j.pharmthera.2013.07.008.

[GERBER A N. Glucocorticoids and thelung[M ] //Advances in Experimental Medicine and Biology. New York: Springer, 2015: 279-298. DOI: 10.1007/978-1-4939-2895-8_12 http://dx.doi.org/10.1007/978-1-4939-2895-8_12

NIU C, LIU N, LIU J, et al . Vitamin A maintains the airway epithelium in a murine model of asthma by suppressing glucocorticoid-induced leucine zipper[J ] . Clin Exp Allergy, 2016, 46(6): 848-860. DOI: 10.1111/cea.12646.

SCHUSTER G U, KENYON N J, STEPHENSEN C B. Vitamin A deficiency decreases and high dietary vitamin A increases disease severity in the mouse model ofasthma[J]. J Immunol, 2008, 180(3): 1834-1842. DOI: 10.4049/jimmunol.180.3.1834.

KOLMERT J, PIÑEIRO-HERMIDA S, HAMBERG M, et al . Prominent release of lipoxygenase generated mediators in a murine house dust mite-induced asthma model[J ] . Prostaglandins Other Lipid Mediat, 2018, 137: 20-29. DOI: 10.1016/j.prostaglandins.2018.05.005.

ZANG N, LI S M, LI W, et al . Resveratrol suppresses persistent airway inflammation and hyperresponsivess might partially via nerve growth factor in respiratory syncytial virus-infected mice[J ] . Int Immunopharmacol, 2015, 28(1): 121-128. DOI: 10.1016/j.intimp.2015.05.031.

GANESAN S, COMSTOCK A T, SAJJAN U S. Barrier function of airway tractepithelium[J]. Tissue Barriers, 2013, 1(4): e24997. DOI: 10.4161/tisb.24997.

WALSH G M. Recent developments in the use of biologics targeting IL-5, IL-4, or IL-13 in severe refractoryasthma[J]. Expert Rev Respir Med, 2018, 12(11): 957-963. DOI: 10.1080/17476348.2018.1520095.

CUI WW, ZHANG P, GU J M, et al . Vitamin A deficiency promotes inflammation by induction of type 2 cytokines in experimental ovalbumin-induced asthma murine model[J ] . Inflammation, 2016, 39(5): 1798-1804. DOI: 10.1007/s10753-016-0415-2.

MARQUEZ H A, CARDOSO W V. Vitamin A-retinoid signaling in pulmonary development anddisease[J]. Mol Cell Pediatr, 2016, 3(1): 28. DOI: 10.1186/s40348-016-0054-6.

LOSSI L, CASTAGNA C, MERIGHI A. Caspase-3 mediated cell death in the normal development of the mammaliancerebellum[J]. Int J Mol Sci, 2018, 19(12): E3999. DOI: 10.3390/ijms19123999.

HU Y H, DONG H M, ZOU M C, et al . TSLP signaling blocking alleviates E-cadherin dysfunction of airway epithelium in a HDM-induced asthma model[J ] . Cell Immunol, 2017, 315: 56-63. DOI: 10.1016/j.cellimm.2017.02.003.

CHEN F, JIANG Z Y, JIANG S Q, et al . Dietary vitamin A supplementation improved reproductive performance by regulating ovarian expression of hormone receptors, caspase-3 and Fas in broiler breeders[J ] . Poult Sci, 2016, 95(1): 30-40. DOI: 10.3382/ps/pev305.

BRUSCOLI S, BIAGIOLI M, SORC INI D, et al . Lack of glucocorticoid-induced leucine zipper (GILZ) deregulates B-cell survival and results in B-cell lymphocytosis in mice[J ] . Blood, 2015, 126(15): 1790-1801. DOI: 10.1182/blood-2015-03-631580.

LOMMATZSCH M. Airwayhyperresponsiveness: new insights into the pathogenesis[J]. Semin Respir Crit Care Med, 2012, 33(6): 579-587. DOI: 10.1055/s-0032-1325617.

SHOSEYOV D, BIBI H, BIESALSKI H, et al . Repeated allergen challenge in rats increases vitamin A consumption[J ] . Chest, 2002, 122(4): 1407-1411. DOI: 10.1378/chest.122.4.1407.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of cinnamaldehyde on Bax/Bak and apoptosis of vascular endothelial cells in diabetic ulcers

Down-regulating HOXA-AS2/miR-20a pathway promotes apoptosis and inhibits invasion and migration of skin squamous carcinoma cells

Lycium barbarum polysaccharide inhibits apoptosis of intestinal epithelial cells through mitochondrial pathway in mice with radiation-induced intestinal injury

Role of PPARγ activation in cell growth inhibition and apoptosis inducement by ampelopsin in breast cancer cells

Related Author

JIN Zheyu

XIE Chenlei

FAN Xinqi

YANG Shu

DONG Ruiyi

BAI Yanyu

DING Yarong

ZHOU Zhongzhi

Related Institution

Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine， Hunan University of Chinese Medicine

Department of Burn Wounds and Plastic Surgery， First Affiliated Hospital of Hunan University of Chinese Medicine

First Department of Characteristic Specialities, Jiangsu Provincial General Hospital of Armed Police

Department of Outpatient, Jiangsu Provincial General Hospital of Armed Police

Department of Dermatology, Jiangsu Provincial General Hospital of Armed Police

⁰