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Rosuvastatin attenuates mucus secretion in a murine model of chronic asthma by inhibiting the gamma-aminobutyric acid type A receptor

ZHU Tao ZHANG Wei WANG Dao-xin HUANG Ni-wen BO Hong DENG Wang DENG Jia

中华医学杂志(英文版)2012,Vol.125Issue(8):1457-1464,8.
中华医学杂志(英文版)2012,Vol.125Issue(8):1457-1464,8.DOI:10.3760/cma.j.issn.0366-6999.2012.08.018

Rosuvastatin attenuates mucus secretion in a murine model of chronic asthma by inhibiting the gamma-aminobutyric acid type A receptor

Rosuvastatin attenuates mucus secretion in a murine model of chronic asthma by inhibiting the gamma-aminobutyric acid type A receptor

ZHU Tao 1ZHANG Wei 1WANG Dao-xin 1HUANG Ni-wen 2BO Hong 3DENG Wang 1DENG Jia1

作者信息

  • 1. Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
  • 2. Department of Respiratory Medicine , West China Hospital, Sichuan University,Chengdu, Sichuan 610041, China
  • 3. Departemnt of Nephrology , West China Hospital, Sichuan University,Chengdu, Sichuan 610041, China
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摘要

Abstract

Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction,pulmonary inflammation and airway remodeling.Current standard therapies for asthma provide symptomatic control,but fail to target the underlying disease pathology.Furthermore,no therapeutic agent is effective in preventing airway remodeling.A substantial amount of evidence suggests that statins have anti-inflammatory properties and immunomodulatory activity.In this study,we investigated the effect of rosuvastatin on airway inflammation and its inhibitory mechanism in mucus hypersecretion in a murine model of chronic asthma.Methods BALB/c mice were sensitized and challenged by ovalbumin to induce asthma.The recruitment of inflammatory cells into bronchoalveolar lavage fluid (BALF) and the lung tissues were measured by Diff-Quik staining and hematoxylin and eosin (H&E) staining.ELISA was used for measuring the levels of IL-4,IL-5,IL-13 and TNF-α in BALF.Periodic acid-Schiff (PAS) staining was used for mucus secretion.Gamma-aminobutyric acid type A receptor (GABAAR)32 expression was measured by means of immunohistochemistry,reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.Results Rosuvastatin reduced the number of total inflammatory cells,lymphocytes,macrophages,neutrophils,and eosinophils recruited into BALF,the levels of IL-4,IL-5,IL-13 and TNF-α in BALF,along with the histological mucus index (HMI) and GABAAR β2 expression.Changes occurred in a dose-dependent manner.Conclusions Based on its ability to reduce the inflammatory response and mucus hypersecretion by regulating GABAAR activity in a murine model of chronic asthma,rosuvastatin may be a useful therapeutic agent for treatment of asthma.

关键词

airway remodeling/asthma/gamma-aminobutyric acid type A receptorβ2/mucus/rosuvastatin

Key words

airway remodeling/asthma/gamma-aminobutyric acid type A receptorβ2/mucus/rosuvastatin

引用本文复制引用

ZHU Tao,ZHANG Wei,WANG Dao-xin,HUANG Ni-wen,BO Hong,DENG Wang,DENG Jia..Rosuvastatin attenuates mucus secretion in a murine model of chronic asthma by inhibiting the gamma-aminobutyric acid type A receptor[J].中华医学杂志(英文版),2012,125(8):1457-1464,8.

基金项目

This study was partially supported by the National Natural Science Foundation of China (No.30971303). (No.30971303)

中华医学杂志(英文版)

OACSCDCSTPCDMEDLINESCI

0366-6999

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