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布地奈德对哮喘小鼠模型中缺氧诱导因子-1α和血管内皮生长因子表达及气道重塑的影响

[Effects of budesonide on HIF-1α and VEGF expression and airway remodeling in an asthmatic mouse model].

作者信息

Sun Yan, Wang Jin-Rong, Han Xiu-Zhen, Li Hua-Bing, Sun Li-Feng, Chen Xing, Feng Yi-Zhen

机构信息

Department of Pediatrics, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2012 Aug;14(8):622-7.

Abstract

OBJECTIVE

To study the effects of budesonide on hypoxia inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) expression, angiogenesis and airway remodeling in the chronic asthmatic mouse model.

METHODS

Thirty female BALB/c mice were randomly divided into normal control, asthma model and treatment groups (10 in each group).The asthmatic mouse model was established via OVA challenge test. Mice in the treatment group were administered with aerosol budesonide (100 μg/kg) an hour before the OVA challenge test from the 28th day. Mice in the control group were treated with PBS instead of OVA. Hematoxylin and eosin staining was performed to observe thickness of the airway wall. Masson staining was used for examing collagen deposition of lung tissues. Angiogenesis and HIF-1α and VEGF expression were measured using immunohistochemistry and Western blot. The relationship of airway wall thickness and vessel area to HIF-1α and VEGF expression was investigated.

RESULTS

Vessel area, collagen deposition of lung tissues and airway wall thickness increased in the asthma model group. Levels of HIF-1α and VEGF were also elevated. Administration of budesonide significantly reduced angiogenesis, collagen deposition of lung tissues and airway wall thickening, as well as expression of HIF-1α and VEGF. The vessel area and airway wall thickness were positively correlated with expression of HIF-1α and VEGF. A positive correlation was also found between the expression of HIF-1α and VEGF.

CONCLUSIONS

Budesonide can decease angiogenesis and airway remodeling by inhibiting HIF-1α and VEGF expression in asthmatic mice.

摘要

目的

研究布地奈德对慢性哮喘小鼠模型中缺氧诱导因子1α(HIF-1α)和血管内皮生长因子(VEGF)表达、血管生成及气道重塑的影响。

方法

将30只雌性BALB/c小鼠随机分为正常对照组、哮喘模型组和治疗组(每组10只)。通过卵清蛋白(OVA)激发试验建立哮喘小鼠模型。从第28天起,治疗组小鼠在OVA激发试验前1小时给予布地奈德气雾剂(100μg/kg)。对照组小鼠用PBS代替OVA进行处理。采用苏木精-伊红染色观察气道壁厚度。采用Masson染色检测肺组织胶原沉积。采用免疫组织化学和蛋白质印迹法检测血管生成及HIF-1α和VEGF表达。研究气道壁厚度和血管面积与HIF-1α和VEGF表达的关系。

结果

哮喘模型组血管面积、肺组织胶原沉积和气道壁厚度增加。HIF-1α和VEGF水平也升高。给予布地奈德可显著减少血管生成、肺组织胶原沉积和气道壁增厚,以及HIF-1α和VEGF表达。血管面积和气道壁厚度与HIF-1α和VEGF表达呈正相关。HIF-1α和VEGF表达之间也呈正相关。

结论

布地奈德可通过抑制哮喘小鼠中HIF-1α和VEGF表达来减少血管生成和气道重塑。

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