组蛋白去乙酰化酶在肺部疾病治疗中的研究进展  

The advance of histone deacetylases in the treatment of pulmonary diseases

作　　者：许慧[1] 洪虹[1] 孟欣 张海燕[1] XU Hui;HONG Hong;MENG Xin;ZHANG Hai-yan(Department of Geriatrics of the First Affiliated Hospital,School of Life Sciences,China Medical University,Shenyang 110122,China;Department of Biochemistry and Molecular Biology,School of Life Sciences,China Medical University,Shenyang 110122,China)

机构地区：[1]中国医科大学附属第一医院老年医学科,辽宁沈阳110001 [2]中国医科大学生命科学学院生物化学与分子生物学教研室,辽宁沈阳110122

出　　处：《解剖科学进展》2023年第3期333-336,共4页Progress of Anatomical Sciences

基　　金：国家自然科学基金(81572831)。

摘　　要：肺部疾病发生、发展与组蛋白去乙酰化酶(HDACs)家族密切相关,HDACs抑制剂通过抑制哮喘相关炎症因子表达等途径缓解哮喘气道的炎症、重塑和高反应,通过影响NF-κB炎症通路的激活水平治疗慢性阻塞性肺疾病,通过调控Akt磷酸化水平和影响PP2A/HDAC4通路等途径治疗肺纤维化,通过降低心肌血管内皮细胞中VEGF等血管生成因子表达治疗肺动脉高压,通过影响T细胞介导的免疫调节、线粒体凋亡等途径抑制肺癌发生、发展。但在不同肺部疾病中,HDACs各成员的表达分布、表达水平并不相同,因此,明确HDACs抑制剂的作用机制和靶点,有针对地选取HDACs抑制剂有望为肺部疾病的治疗提供新突破。The occurrence and development of lung diseases are closely related to the histone deacetylases(HDACs),HDACs inhibitors alleviate inflammation,remodeling and hyperresponsiveness of airway via inhibiting the expression of asthma related inflammatory factors,have therapeutic effect on chronic obstructive pulmonary disease via activating NF-kB inflammatory pathway,and on pulmonary fibrosis via Akt phosphorylation and PP2A/HDAC4 pathway,reduce the expression of VEGF and other angiogenic factors in myocardial endothelial cells for the treatment of pulmonary hypertension,inhibit lung cancer occurrence and development via affecting T cell-mediated immune regulation and mitochondrial apoptosis.The distribution and expression level of HDACs varies in different kinds of lung diseases.Therefore,it is important to discover effective HDACs inhibitors in the treatment of lung diseases.

关 键 词：组蛋白去乙酰化酶 肺部疾病 血管生成因子 肺纤维化 肺动脉高压 免疫调节 PP2A HDACS 

分 类 号：R563[医药卫生—呼吸系统]