β3-肾上腺素受体下调NADPH氧化酶改善心肌肥厚的机制

心肌肥厚是心血管事件的独立危险因素。β-肾上腺素受体（β-AR）家族在心血管系统中发挥了重要的调节作用。近年研究显示除了传统的β1/β2-AR之外，心脏还存在β3-AR。我们的前期研究结果表明β3-AR可能通过减轻氧化应激对压力负荷所致的心肌肥厚发挥重要的保护作用，但其机制尚不清楚。还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶介导的氧化应激是心肌肥厚发生的重要机制，β3-AR是否通过下调NADPH氧化酶改善心肌肥厚目前尚未见报道。本研究通过主动脉弓缩窄术建立小鼠心肌肥厚模型，分别观察β3-AR激活、阻断及基因敲除对心脏结构和功能的影响；研究β3-AR与NADPH氧化酶介导的氧化应激的关系及其对NADPH氧化酶的重要亚基和下游信号通路的调节作用；并利用NADPH氧化酶抑制剂从反面进一步证实下调NADPH氧化酶是其改善心肌肥厚的重要机制，为β3-AR防治心肌肥厚提供新的理论和实验依据。

Cardiac hypertrophy is an independent risk factor of cardiovascular events. β-adrenergic receptor (β-AR)family plays a vital role in the modulation of cardiovascular system. Recently it is demonstrated that besides traditional β1/β2 AR, there is another one, β3-AR expressed in the heart. Our previous data showed that β3-AR play an important cardioprotective role in pressure overload induced hypertrophy. However,the mechanisms are still unclear.Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mediated oxidative stress has been approved to play an important role in the progression of cardiac hypertrophy while whether β3-AR downregulates NADPH oxidase to protect cardiac hypertrophy has not been reported before.Thus, in the present study,mice underwent transverse aortic constriction to set the pressure overload induced cardiac hypertrophy and model. We use this model to observe the effect of β3-AR activation, inhibition or knockout on cardiac configuration and function respectively; to study the relationship between β3-AR and NADPH oxidase mediated oxidative stress, and it's modulation on the key subunits of NADPH oxidase and the downstream signaling pathway; and then make use of the NADPH oxidase inhibitor to further confirm that downregulation of NADPH oxidase is the important mechanism of β3-AR alleviating cardiac hypertrophy. This study aims to provide new theoretical and experimental evidence for the protective role of β3-AR in cardiac hypertrophy.