β1肾上腺素受体与心衰、高血压和心肌纤维化之间的关系研究进展  

Research advances on the role of β1-adrenergic receptor in heart failure,hypertension and myocardial fibrosis

作　　者：刘小丽[1,2] 邢晓为[3] 黄利华[3] 黄志军[2] 袁洪[1,2] 

机构地区：[1]中南大学药学院,湖南长沙410013 [2]中南大学湘雅三医院临床药理中心,湖南长沙410013 [3]中南大学湘雅三医院医学实验中心,湖南长沙410013

出　　处：《中国药理学通报》2013年第12期1640-1644,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30873126;81273594);国家重点基础研究发展计划(2011CB512001)

摘　　要：β1肾上腺素受体(β1 adrenergic receptor,β1-AR)是心脏组织中肾上腺素受体的主要亚型。β1-AR基因表达变化与心衰、高血压等心血管疾病的发生、发展及治疗密切相关。β1-AR激活后,启动经典的G蛋白-腺苷酸环化酶-环磷酸腺苷-蛋白激酶A(Gs-AC-cAMP-PKA)信号转导通路。但当机体发生病理性改变时,β1-AR信号通路发生变化。持久兴奋β1-AR,从而激活CaMKII,使心肌收缩增强,心率加快,诱发心肌细胞肥大及凋亡,最终导致心肌重塑、心肌收缩及舒张功能下降。深入了解β1-AR调控在心衰、高血压等心血管疾病发病过程中的分子机制及β1-AR基因多态性和甲基化对个体化治疗的影响,将为临床治疗心血管疾病制定合理化用药方案提供依据和指导。β1-Adrenergic receptor （β1-AR） is the major sub- type of adrenergic receptors in heart tissue. The level of ~I-ARgene expression is closely related to the development and treat- ment of heart failure, hypertension and other cardiovascular dis- eases. Upon activation, β1-AR stimulates the classic Gs-AC- cAMP-PKA signaling transduction pathway. When the organism has pathological changes, the signaling pathway ahers. Persistent β1-AR stimulation activates CaMKII, leading to an increase in myocardial contractility and heart rate. In turn, these induce cardiomyocyte hypertrophy and apoptosis, leading to myocardial remodeling and decrease of the myocardial function finally. In-sights into the molecular mechanism of β1-AR expression regula- tion on the pathogenesis of heart failure, hypertension and other cardiovascular diseases, and the effect of β1-AR gene polymor- phism and methylation status in individualized treatment, will provide reasonable evidence and guidance for the clinical treat- ment of cardiovascular diseases.

关 键 词：Β1肾上腺素受体 心力衰竭 心肌纤维化 高血压 CAMKII 机制 治疗 

分 类 号：R-05[医药卫生] R392.11