Belvisi Maria G, Hele David J
National Heart & Lung Institute, Faculty of Medicine, Imperial College, Respiratory Pharmacology Group, Guy Scadding Building, Dovehouse St, London SW3 6LY, UK.
Chest. 2008 Jul;134(1):152-7. doi: 10.1378/chest.08-0019.
Inflammatory diseases of the lung such as asthma and COPD represent a major worldwide health problem. There are potent antiinflammatory drugs available to treat asthma, such as the glucocorticoids, but these produce unwanted side effects and exhibit limited efficacy in the treatment of COPD. The identification of the peroxisome proliferator-activated receptors (PPARs) PPARgamma, PPARalpha, and PPARdelta opened up a new avenue of research as it was discovered that they exhibited antiinflammatory and immunomodulatory properties. In animal models of allergic and occupational asthma, COPD and pulmonary fibrosis PPARs are involved in the inflammatory cascade, and treatment with PPAR agonists reduces inflammation and results in beneficial outcomes. The actions of PPARgamma and PPARalpha activation are thought to be due to their ability to down-regulate proinflammatory gene expression and inflammatory cell functions, and as such makes them an attractive target for novel drug intervention. PPARdelta has been shown to be involved in wound healing, and its activation may enhance the effects of PPARgamma agonists. The only fly in the ointment is the observation of an increased incidence of cardiovascular events in diabetic patients treated with the PPARgamma agonist rosiglitazone. However, a clinical trial is underway to examine the effect of rosiglitazone in asthma patients, and the outcome of this trial is awaited with much anticipation. PPARs are novel targets for lung disease, and the continued work with PPAR agonists may result in a potential new treatment for these chronic inflammatory lung diseases.
诸如哮喘和慢性阻塞性肺疾病（COPD）等肺部炎症性疾病是全球范围内的重大健康问题。有强效抗炎药物可用于治疗哮喘，如糖皮质激素，但这些药物会产生不良副作用，且在治疗COPD方面疗效有限。过氧化物酶体增殖物激活受体（PPARs）中的PPARγ、PPARα和PPARδ的发现开辟了一条新的研究途径，因为人们发现它们具有抗炎和免疫调节特性。在变应性和职业性哮喘、COPD及肺纤维化的动物模型中，PPARs参与炎症级联反应，用PPAR激动剂治疗可减轻炎症并产生有益结果。PPARγ和PPARα激活的作用被认为是由于它们能够下调促炎基因表达和炎症细胞功能，因此使其成为新型药物干预的有吸引力的靶点。PPARδ已被证明参与伤口愈合，其激活可能增强PPARγ激动剂的作用。唯一美中不足的是，在用PPARγ激动剂罗格列酮治疗的糖尿病患者中观察到心血管事件发生率增加。然而，一项关于罗格列酮对哮喘患者影响的临床试验正在进行中，人们对该试验的结果满怀期待。PPARs是肺部疾病的新型靶点，对PPAR激动剂的持续研究可能会为这些慢性炎症性肺部疾病带来一种潜在的新治疗方法。
