P2X7与呼吸系统炎症性疾病的研究进展

Advance in the research on P2X7 and inflammatory respiratory diseases

P2X7是目前已知的ATP受体中最为关键的一个亚型,近年来,国内外研究证明P2X7信号通路与IL-1β、IL-18等几种炎症因子的产生路径相偶联,其与炎症相关疾病的关系得到密切关注,目前以此受体为治疗靶点的药物已进入临床试验阶段,该类药物表现出的疗效和安全性让人振奋。现阶段国内对P2X7的研究主要集中于神经系统相关疾病,对于呼吸系统炎症性疾病,特别是哮喘、慢性阻塞性肺病(chronic obstructive pulmonarydisease,COPD)及肺癌等的研究少见报道。本文将近年来P2X7与呼吸系统炎症性疾病的研究进展进行归纳,总结其结构、分布、生物学活性以及与哮喘、COPD及肺癌等呼吸系统炎症性疾病之间的关系,并概述拮抗P2X7的相关药物的研究进展。

P2X7 is the most important subtype of the ATP receptors known so far. Recent investigations showed that the downstream signaling pathway of P2X7 is coupled with several key inflammatory molecules including IL-1β and IL-18, this suggests P2X7 might have roles in the inflammatory diseases. Moreover, attenuation of P2X7 by selective antagonists in vitro and knockout mice in vivo reducing the inflammatory response indicated that P2X7 is a potential therapeutic target for inflammatory diseases. However, most previous studies on P2X7 were focused on nerve system diseases most, while its effects in inflammatory respiratory diseases, especially in asthma, chronic obstructive pulmonary disease （COPD） and lung cancer have been poorly investigated. In this paper, we reviewed the research progress on the structure, distribution, biological activities of P2X7 and its relationship with inflammatory respiratory diseases including asthma, COPD and lung cancer, along with the development of P2X7 antagonist as therapeutics.