磷酸二酯酶抑制剂治疗炎性肠病的研究进展

Research progress of phosphodiesterase inhibitors in inflammatory bowel disease treatment

炎性肠病是一种慢性复发性肠道炎性疾病,尚无理想治疗方法。磷酸二酯酶(PDE)通过介导细胞内第二信使环磷酸腺苷和环磷酸鸟苷的水解影响细胞内信号级联反应,从而调控多种病理、生理过程。近年来,一系列研究结果显示,PDE抑制剂如多种PDE4抑制剂、PDE5抑制剂(西地那非、他达拉非及伐地那非)、PDE3抑制剂(西洛他唑)、PDE9抑制剂(PF-04447943)、PDE3/PDE4双抑制剂(pumafentrine)对实验性结肠炎具有改善作用;PDE4抑制剂阿普司特在临床试验中较替托司特的治疗优势更明显。本文就PDE抑制剂在炎性肠病治疗中的研究进展进行综述。

Inflammatory bowel disease is a recurrent chronic intestinal inflammatory disease with unknown etiology and no effective treatment.Phosphodiesterase(PDE)regulates a variety of physiological and pathophysiological processes by mediating the hydrolysis of intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate.In recent years,a series of researches suggest that PDE inhibitors such as several PDE4 inhibitors,PDE5 inhibitors(sildenafil,tadalafil and vardenafil),PDE3 inhibitors(cilostazol),PDE9 inhibitor(PF-04447943)and PDE3/PDE4 double inhibitor(pumafentrine)have ameliorating effect on experimental colitis in animals.In clinical trials,PDE4 inhibitor apremilast showed more therapeutic advantage than tetomilast.This article reviews the recent research progress of PDE inhibitors in treatment of inflammatory bowel disease.