窦房结自律性受到心脏昼夜节律钟调节，其中节律钟基因BMAL1低表达是缓慢性心律失常 （BA）发病的关键分子基础。申请人前期研究证明BMAL1下游基因SCN5A、HCN4低表达可导致窦房结自律性降低而触发BA，临床疗效确切的元姜方通过上调SCN5A、HCN4蛋白表达，增加细胞内钙浓度，提高窦房结自律性，但其机制是否与作用于BMAL1调节心脏昼夜节律钟有关尚无研究。故提出科学假说：元姜方通过上调BMAL1/SCN5A/HCN4表达，调控心脏昼夜节律钟，提高窦房结自律性。本研究建立缺血再灌注损伤窦房结区BA大鼠模型、糖氧剥夺诱导窦房结细胞损伤模型，从心率、窦房传导时间、窦房结恢复时间、窦房结有效不应期观察疗效，从起搏电流强度、BMAL1示踪节律钟在体荧光强度、BMAL1/SCN5A/HCN4基因及蛋白表达变化探索机制，阐明元姜方提高窦房结自律性的作用机理，为其临床应用提供实验依据。

The automaticity of sinoatrial node is regulated by cardiac circadian clock, in which the low expression of circadian clock gene BMAL1 is the key molecular basis for the pathogenesis of Bradycardiac arrhythmia (BA). The applicant's previous studies have proved that the low expression of SCN5A and HCN4, both are BMAL1 downstream genes, can lead to the decrease of sinoatrial node automaticity and trigger BA. Yuan Jiang formula, an empirical formula of Weng Weiliang, can increase the intracellular calcium concentration and improve the automaticity of sinoatrial node by up-regulating the expression of SCN5A and HCN4 protein. However, whether the mechanism is related to the regulation of cardiac circadian clock through BMAL1 has not been studied. Therefore, scientific hypothesis is put forward: Yuanjiang prescription can regulate the cardiac circadian clock and improve the automaticity of sinoatrial node by up-regulating the expression of BMAL1/SCN5A/HCN4. In this study, with establishment of the BA rat model of sinoatrial node injury induced by ischemia-reperfusion and the sinoatrial node cell injury model induced by glucose and oxygen deprivation, the heart rate(HR), sinoatrial conduction time(SACT), sinoatrial node recovery time,(SNRT) sinoatrial node effective refractory period(ERP), If intensity, BMAL1 tracer center and cardiac circadian clock in vivo and BMAL1/SCN5A/HCN4 expression were measured every 6 hours in a single day. So as to clarify the mechanism of Yuanjiang formula in improving the sinoatrial node automaticity and provide experimental basis for its clinical application.