选择性磷酸二酯酶抑制剂罗氟司特在慢性阻塞性肺疾病抗炎作用的研究进展

Reseach advance of the anti-inflammatory effect of selective phosphodiesterase 4 inhibitor Roflumilast inchronic obstructive pulmonary disease

磷酸二酯酶4（Phosphodiesterase4，PDE4）、特异性水解环磷酸腺苷（cyclicadenosinemonophosphate，cAMP），广泛存在于多种炎症细胞及结构细胞中。选择性抑制PDE4使细胞内cAMP浓度增加，呈现抗炎作用。第二代PDE4抑制剂罗氟司特（roflumilast）具有抑制中性粒细胞、T细胞、巨噬细胞等多种炎症细胞及TNF-α、LTB4、活性氧、IFN-r等多种炎症介质的抗炎作用，成为第一个应用于慢性阻塞性肺疾病临床治疗的PDE4抑制剂。罗氟司特的抗炎效果可能与炎症类型、药物剂量、免疫形式等影响因素有关。

Phosphodiesterase 4 is a cyclic adenosine monophosphate （ cAMP ）-specific enzyme which has a ubiquitous distribution in inflammatory and structural cells. Selective PDE4 inhibitors prevent the hydrolysis of cAMP, leading to broad spectrum antiinflammatory effects. Among these drugs, the second-generation PDE4 inhibitor Roflumilast was the first to be developed and approved for market （in Europe and USA） as a COPD therapy. Roflumilast demonstrated great suppressing effects on a wide range of inflammatory cells, such as neutrophils, T lymphocytes, macrophages, eosinophils, and also on a variety of inflammatory mediators, such as TNF-α, LTB4, IFN-r and reactive oxygen species. The anti-inflammatory effect of roflumilast may be related to the inflammatory type, drug dose and immune form.