哮喘治疗中β_(2)-AR激动药诱发受体脱敏的发生机制及预防进展  

Mechanism and prevention progress of receptor desensitization induced byβ_(2)-AR agonists in the treatment of asthma

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作  者:段俊亚 张岩[1,2] 宋桂华[1] 陈小松[1] 郭彦荣[1] 周璇 陈新颖 DUAN Junya;ZHANG Yan;SONG Guihua;CHEN Xiaosong;GUO Yanrong;ZHOU Xuan;CHEN Xinying(Dept.of Pediatrics,the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450003,China;School of Pediatrics,Henan University of Chinese Medicine,Zhengzhou 450003,China)

机构地区:[1]河南中医药大学第一附属医院儿科医院,郑州450003 [2]河南中医药大学儿科医学院,郑州450003

出  处:《中国药房》2024年第15期1910-1914,共5页China Pharmacy

基  金:国家自然科学基金面上项目(No.81873338);河南省医学科技攻关计划联合共建项目(No.LHGJ20230687);河南省“双一流”创建学科中医学科学研究专项(No.HSRP-DFCTCM-2023-8-26)。

摘  要:β_(2)-肾上腺素受体(β_(2)-AR)激动药作为治疗支气管哮喘(以下简称“哮喘”)的一线药物,在临床中广泛应用,然而长期使用可导致β_(2)-AR脱敏,降低其临床疗效,致使部分哮喘患者症状控制欠佳。β_(2)-AR激动药引起β_(2)-AR脱敏的机制主要包括慢速脱敏(与气道黏膜β_(2)-AR密度减小有关)和快速脱敏(与刺激性G蛋白脱偶联机制有关)。环磷酸腺苷(cAMP)-蛋白激酶A和cAMPcAMP激活的交换蛋白信号通路与β_(2)-AR脱敏过程关系密切。糖皮质激素、过氧化物酶体增殖物激活受体γ激动药、ASM-024、中药单药及成方等与β_(2)-AR激动药联合使用时能改善β_(2)-AR的敏感性,从而更好地控制哮喘症状。β_(2)-adrenergic receptor(β_(2)-AR)agonists are widely used as first-line drugs in the treatment of bronchial asthma(hereinafter referred to as“asthma”),but long-term use can lead toβ_(2)-AR desensitization and reduce its clinical efficacy,resulting in poor symptom control of some asthma patients.The mechanism ofβ_(2)-AR desensitization induced byβ_(2)-AR agonists mainly includes slow hyposensitization(related to the decrease ofβ_(2)-AR density in airway mucosa)and rapid hyposensitization(related to the mechanism of stimulatory G protein decoupling).Cyclic adenosine monophosphate(cAMP)-protein kinase A and cAMP-exchange protein activated by cAMP signaling pathways are closely related toβ_(2)-AR desensitization.Glucocorticoids,peroxisome proliferator-activated receptor-gamma agonists,ASM-024,Chinese medicine monotherapies and formulations,when combined withβ_(2)-AR agonists,can improve the sensitivity ofβ_(2)-AR,so as to better control asthma symptoms.

关 键 词:支气管哮喘 β_(2)-肾上腺素受体激动药 脱敏 发生机制 预防作用 

分 类 号:R974.3[医药卫生—药品] R562.25[医药卫生—药学]

 

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