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在运动或应激状况下,β肾上腺素受体(βAR)的激活可有力地增加心输出量。然而,心衰时持续的βAR激活可导致心肌肥大、心肌细胞凋亡等病理性心肌重塑过程。目前认为,心肌细胞表面存在结构、效应特异的三种βAR亚型:β1、β2及β3AR。β1AR可激活经典的Gs-AC-cAMP-PKA信号通路;β2AR同时激活Gs-AC-cAMP-PKA及Giα-Giβγ-PI3K-Akt信号通路;而β3AR则通过Gi-eNOS-NO-cGMP介导负性变力效应。目前研究表明:心衰时长期的β1AR激活可通过Gs-Ca2+-CaMKⅡ通路导致心肌肥大、心肌细胞凋亡等病理性心肌重塑过程;而持续的β2AR刺激则通过Giα-Giβγ-PI3K-Akt通路产生抗心肌肥大、心肌细胞凋亡效应。对心衰时上述βAR亚型的信号转导、效应的深入认识不仅对βAR阻滞剂治疗慢性心衰提供了分子和细胞机制的依据,而且为我们带来了一些治疗慢性心衰的新思路。
Activation of the beta adrenergic receptor (AR) strongly increases cardiac output in exercise or stress conditions. However, sustained βAR activation during heart failure can lead to pathological myocardial remodeling, such as cardiac hypertrophy and cardiomyocyte apoptosis. Currently, there are three types of βAR subtypes: β1, β2 and β3AR, which are structural and effector. β1AR activates the classical Gs-AC-cAMP-PKA signaling pathway; β2AR activates both Gs-AC-cAMP-PKA and Giα-Giβγ-PI3K-Akt signaling pathway; while β3AR is mediated by Gi-eNOS-NO-cGMP Sexual variation effect. The present study shows that long-term β1AR activation during heart failure leads to cardiac myocyte hypertrophy and cardiomyocyte apoptosis through Gs-Ca2 + -CaMKⅡ pathway, whereas sustained β2AR stimulation via Giα-Giβγ-PI3K-Akt pathway Produce anti-cardiac hypertrophy, cardiomyocyte apoptosis effect. In heart failure, the above-mentioned understanding of the signal transduction and effect of βAR subtypes not only provides a molecular and cellular basis for the treatment of chronic heart failure with βAR blockers, but also brings us some new ideas for the treatment of chronic heart failure .