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白藜芦醇对变应性气道疾病小鼠模型的气道重塑和气道高反应性具有保护作用。

Resveratrol has protective effects against airway remodeling and airway hyperreactivity in a murine model of allergic airways disease.

作者信息

Royce Simon G, Dang William, Yuan Gao, Tran Jenny, El Osta Assam, Karagiannis Tom C, Tang Mimi L K

机构信息

Allergy and Immune Disorders, Murdoch Children's Research Institute, Melbourne, Vic., Australia.

出版信息

Pathobiol Aging Age Relat Dis. 2011;1. doi: 10.3402/PBA.v1i0.7134. Epub 2011 Jun 1.

Abstract

BACKGROUND

New therapies for asthma which can address three main interrelated features of the disease, airway inflammation, airway remodeling and airway hyperreactivity, are urgently required. Resveratrol, a well known red wine polyphenol has received much attention due to its potential anti-aging properties. This compound is an agonist of silent information regulator two histone deacetylases and has many effects that are relevant to key aspects of the pathophysiology of asthma including inflammation, cell proliferation and fibrosis. Therefore, resveratrol may offer a novel asthma therapy that simultaneously inhibits airway inflammation, and airway remodeling which are the main contributors to airway hyperreactivity and irreversible lung function loss.

METHODS

We evaluated the effects of systemic resveratrol treatment in a murine model of chronic allergic airways disease which displays most of the clinicopathological features of severe human asthma. Wild-type Balb/c mice with allergic airways disease were treated with 12.5 mg/kg resveratrol or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell counts and histological examination of lung tissue sections. Further, remodeling was assessed by morphometric analysis and lung function was assessed by invasive plethysmography measurement of airway resistance and dynamic compliance.

RESULTS

Mice treated with resveratrol exhibited reduced tissue inflammation as compared to vehicle treated mice (p<0.05). Additionally, resveratrol treatment resulted in reduced subepithelial collagen deposition as compared to vehicle treated mice (p<0.05) and attenuated airway hyperreactivity (p<0.05).

CONCLUSIONS

These novel findings demonstrate that treatment with resveratrol can reduce structural airway remodeling changes and hyperreactivity. This has important implications for the development of new therapeutic approaches to asthma.

摘要

背景

迫切需要能够针对哮喘的三个主要相互关联特征——气道炎症、气道重塑和气道高反应性的新疗法。白藜芦醇是一种著名的红酒多酚,因其潜在的抗衰老特性而备受关注。该化合物是沉默信息调节因子2组蛋白脱乙酰酶的激动剂,具有许多与哮喘病理生理学关键方面相关的作用,包括炎症、细胞增殖和纤维化。因此,白藜芦醇可能提供一种新的哮喘治疗方法,同时抑制气道炎症和气道重塑,而气道炎症和气道重塑是气道高反应性和不可逆肺功能丧失的主要原因。

方法

我们在一种慢性过敏性气道疾病的小鼠模型中评估了全身白藜芦醇治疗的效果,该模型表现出严重人类哮喘的大多数临床病理特征。患有过敏性气道疾病的野生型Balb/c小鼠接受12.5mg/kg白藜芦醇或载体对照治疗。通过支气管肺泡灌洗细胞计数和肺组织切片的组织学检查评估气道炎症。此外,通过形态计量分析评估重塑,通过有创体积描记法测量气道阻力和动态顺应性评估肺功能。

结果

与接受载体治疗的小鼠相比,接受白藜芦醇治疗的小鼠组织炎症减轻(p<0.05)。此外,与接受载体治疗的小鼠相比,白藜芦醇治疗导致上皮下胶原沉积减少(p<0.05),气道高反应性减弱(p<0.05)。

结论

这些新发现表明,白藜芦醇治疗可减少气道结构重塑变化和高反应性。这对哮喘新治疗方法的开发具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a7f/3417665/caa0a530cd2b/PBA-1-7134-g001.jpg

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