维生素A联合地塞米松对哮喘小鼠气道上皮结构和功能的影响

胡婕; 邹文静; 王韵婷; 符州; 代继宏; 牛超

doi:10.16016/j.1000-5404.201906118

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维生素A联合地塞米松对哮喘小鼠气道上皮结构和功能的影响

基础医学 | 更新时间：2026-01-09

- 维生素A联合地塞米松对哮喘小鼠气道上皮结构和功能的影响
- Effects of vitamin A combined with dexamethasone on airway epithelium structure and function in asthmatic mice
- 第三军医大学学报 2019年41卷第22期页码：2158-2165
- 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：
  
  [牛超，E-mail:niuchaoo1985@126.comNIU Chao, E-mail: niuchaoo1985@126.com
- 基金信息：
  
  国家自然科学基金青年科学基金项目(81600022)
- DOI：10.16016/j.1000-5404.201906118
  中图分类号： R562.25;R677.11;R977.21
- 收稿：2019-06-18，
  
  修回：2019-07-14，
  
  纸质出版：2019-11-30
- 稿件说明：
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胡婕, 邹文静, 王韵婷, 等. 维生素A联合地塞米松对哮喘小鼠气道上皮结构和功能的影响[J]. 第三军医大学学报, 2019,41(22):2158-2165.

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.
胡婕, 邹文静, 王韵婷, 等. 维生素A联合地塞米松对哮喘小鼠气道上皮结构和功能的影响[J]. 第三军医大学学报, 2019,41(22):2158-2165. DOI： 10.16016/j.1000-5404.201906118.

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

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