磷酸二酯酶4抑制剂作为特发性肺纤维化药物治疗的可能性

The possibility of phosphodiesterase 4 inhibitors as drug therapy for idiopathic pulmonary fibrosis

特发性肺纤维化(IPF)是一种进行性、不可逆和典型的慢性纤维化肺病,近年来,对IPF的病理生理学认识、临床诊断和治疗有了显著进展。但至目前为止,仍然没有治愈IPF的方法。第二信使环磷酸腺苷(cAMP)在IPF的发展过程中抑制成纤维细胞增殖或向肌成纤维细胞分化。磷酸二酯酶4(phosphodiesterase 4,PDE4)是肺成纤维细胞中主要的cAMP降解酶,在纤维化的进展中上调,PDE4抑制剂在IPF模型中具有体内和体外抗纤维化作用。此外,PDE4广泛参与炎症过程,炎症过程在IPF的发病机制中也很活跃。因此,抑制PDE4是一种潜在的治疗IPF的方法。本文综述了IPF的发病机制和PDE4抑制剂在治疗IPF中的生理功能。

Idiopathic pulmonary fibrosis(IPF)is a progressive,irreversible and typical chronic fibrotic lung disease.In recent years,significant progress has been made in the pathophysiology,clinical diagnosis and treatment of IPF.However,to date,there is still no cure for IPF.The second messenger cyclic adenosine monophosphate(cAMP)inhibits fibroblast proliferation or differentiation into myofibroblasts during the development of IPF.Phosphodiesterase 4(PDE4)is a major camp-degrading enzyme in lung fibroblasts,which is up-regulated during the progression of fibrosis.PDE4 inhibitors have anti-fibrosis effects in vivo and in vitro in IPF models.In addition,PDE4 is widely involved in inflammatory processes,which are also active in the pathogenesis of IPF.Thus,PDE4 inhibition is a potential therapeutic approach for IPF.This article reviews the pathogenesis of IPF and the physiological function of PDE subtype 4 inhibitors in the treatment of IPF.