HDACs及其抑制剂对急性肺损伤调控作用的研究进展  

Research progress of HDACs and associated inhibitors on regulation of acute lung injury

作　　者：赖凯 高明朗 李宁[1] 耿庆[1] LAI Kai;GAO Ming-lang;LI Ning;GENG Qing(Dept of Thoracic Surgery,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院胸外科,湖北武汉430060

出　　处：《中国药理学通报》2023年第12期2216-2221,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81770095,81700093,8210082163);中央高校基本科研专项基金(No 2042021kf0081);湖北省自然科学基金创新群体项目(No 2020CFA027)。

摘　　要：急性肺损伤(acute lung injury,ALI)和其最极端的形式急性呼吸窘迫(acute respiratory distress syndrome,ARDS)是一种高发病率和死亡率的肺部疾病。因其病理生理过程及调节机制非常复杂,目前尚无有效的治疗药物。组蛋白去乙酰化酶(HDACs)是一类具有去乙酰化酶活性的家族蛋白,研究表明,HDACs参与调控ALI/ARDS的病理生理过程,包括对炎症反应、内皮细胞通透性、氧化应激、肺泡液清除和肺组织修复等过程有调节作用,同时,使用HDACs抑制剂(HDACIs)能对ALI/ARDS产生干预作用。该文就HDACs及HDACIs调控ALI/ARDS病理生理过程及其机制进行详细阐述,以期为HDACs靶向药物的临床应用提供依据和参考,并为后续研究HDACs调控ALI/ARDS提供方向。Acute lung injury(ALI)and its most extreme form acute respiratory distress syndrome(ARDS)are lung diseases with high morbidity and mortality.There is no effective therapeutic intervention until now for its complicated pathophysiological processes and sophisticated regulatory mechanism.Histone deacetylases(HDACs)are a family of proteins with deacetylase activity.Studies have shown that HDACs are involved in the pathophysiological processes of ALI/ARDS,including inflammatory responses,endothelial permeability,oxidative stresses,alveolar fluid clearance and lung tissue repairment.Simultaneously,the use of HDACs inhibitors(HDACIs)can interfere with ALI/ARDS progression.In this review we describe and summarize the pathophysiological processes and the underlying mechanisms in ALI/ARDS regulated by HDACs and HDACIs in detail,in order to provide the basis for the clinical application of HDACs-targeted agents and indicate directions for future study.

关 键 词：急性肺损伤 组蛋白去乙酰化酶 组蛋白去乙酰化酶抑制剂 炎症 内皮细胞通透性 氧化应激 肺泡液清除 肺组织修复 

分 类 号：R-05[医药卫生] R322.35R341.27R345R563.8R977.3