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慢性阻塞性肺病药物治疗靶点及其药物研发进展

Progress in therapeutic targets and development of drugs against chronic obstructive pulmonary disease

  • 摘要: 慢性阻塞性肺病(chronic obstructive pulmonary disease, COPD)是一种以气流受限为主要特征的慢性呼吸道疾病,它与气道和肺部对有害气体或有毒颗粒的慢性炎性反应密切相关,并且有可能进一步发展为肺心病和呼吸衰竭。COPD发病机制复杂,目前普遍认为COPD是多种基因遗传与环境因素相互作用的结果,且尚无安全有效药物用于治疗该疾病。本文从氧化应激、蛋白酶/抗蛋白酶失衡、免疫机制、细胞衰老和细胞修复机制、细胞坏死和细胞自噬等方面综述了COPD的发病机制,并分别介绍了潜在的治疗靶点以及相关药物的研究进展,主要包括β2受体激动剂、毒蕈碱拮抗剂、茶碱及其衍生物、靶向炎症介质的药物、蛋白酶抑制剂、激酶抑制剂、PED4抑制剂、腺苷受体调节剂、抗氧剂等,以期为COPD的新药研发提供参考。

     

    Abstract: Chronic obstructive pulmonary disease (COPD), characterized by airflow constraint, is a chronic respiratory disease closely related to the chronic inflammatory response of the airways and lungs to harmful gases or toxic particles, which may further develop into pulmonary heart disease and respiratory failure.At present the complex pathogenesis of COPD is considered to be the result of the interaction of a variety of genetic and environmental factors, and there is stiu no safe and effective drug for the treatment. This article reviews the pathogenesis of COPD from such aspects as oxidative stress, protease/antiprotease imbalance, immune mechanism, cell aging and cell repair mechanism, cell necrosis and autophagy,withan introduction to the potential targets and clinical research progress of related drugs, including β2 receptor agonists, muscarinic antagonists, theophylline and its derivatives, drugs targeting inflammatory mediators, protease inhibitors, kinase inhibitors, PED4 inhibitors, glandular glycoside receptor modulators,and antioxidants, which may provide some reference for the development of new drugs for COPD.

     

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