促血管生成素-1可以阻止哮喘气道炎症及高反应性

2008/09/28

    促血管生成素在血管形成及重塑中发挥了重要作用,促血管生成素-1(Ang-1)可降低血管通透性,降低粘附分子表达及细胞因子生成,因此可以预见给予Ang-1治疗对哮喘有保护性作用。
    雅典学者首先建立由卵白蛋白致敏激发的过敏性气道疾病动物模型,可以看到Ang-1 mRNA及蛋白水平的降低;鼻内给予Ang-1治疗可阻止OVA诱导的嗜酸性粒细胞肺浸润,削弱IL-5、IL-13的增加,减少eotaxin和VCAM-1的表达,可逆转OVA诱导的组织阻力的提高,改善肺功能。
    文章结论:哮喘中Ang-1水平降低,给予Ang-1治疗可防止气道反应性的提高,改善气道炎症,因此在哮喘治疗上可能具有一定价值。
 
                           (农英  卫生部中日友好医院呼吸内科 100029 摘译)
                    (Am J Respir Crit Care Med.2008 ;177(12):1314-1321)


Angiopoietin-1 protects against airway inflammation and hyperreactivity in asthma.
 
Simoes DC, Vassilakopoulos T, Toumpanakis D, Petrochilou K, Roussos C, Papapetropoulos A.
 
G. P. Livanos and M. Simou Laboratories, Evangelismos Hospital, Department of Critical Care and Pulmonary Services, University of Athens School of Medicine, Athens, Greece 10675.
 
RATIONALE: The angiopoietins (Ang) comprise a family of growth factors mainly known for their role in blood vessel formation and remodeling. The best-studied member, Ang-1, exhibits antiapoptotic and antiinflammatory effects. Although the involvement of Ang-1 in angiogenesis is well recognized, little information exists about its role in respiratory physiology and disease. On the basis of its ability to inhibit vascular permeability, adhesion molecule expression, and cytokine production, we hypothesized that Ang-1 administration might exert a protective role in asthma.
OBJECTIVES: To determine changes in the expression of Ang and to assess the ability of Ang-1 to prevent the histologic, biochemical, and functional changes observed in an animal model of asthma. Methods: To test our hypothesis, a model of allergic airway disease that develops after ovalbumin (OVA) sensitization and challenge was used.
MEASUREMENTS AND MAIN RESULTS: Ang-1 expression was reduced at the mRNA and protein levels in lung tissue of mice sensitized and challenged with OVA, leading to reduced Tie2 phosphorylation. Intranasal Ang-1 treatment prevented the OVA-induced eosinophilic lung infiltration, attenuated the increase in IL-5 and IL-13, and reduced eotaxin and vascular cell adhesion molecule 1 expression. These antiinflammatory actions of Ang-1 coincided with higher levels of IkappaB and decreased nuclear factor-kappaB binding activity. More importantly, Ang-1 reversed the OVA-induced increase in tissue resistance and elastance, improving lung function.
CONCLUSIONS: We conclude that Ang-1 levels are decreased in asthma and that administration of Ang-1 might be of therapeutic value because it prevents the increased responsiveness of the airways to constrictors and ameliorates inflammation.
 


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