基于心肌细胞β1-AR通路探讨脉神同调法对交感型阵发性房颤大鼠的作用  

Exploration of the Effect of Maishen Tongtiao Method on Sympathetic Paroxysmal Atrial Fibrillation in Rats Based on theβ1-AR Pathway of Myocardial Cells

作　　者：胡影 陈兴娟 吴怡茹 程晓振 李思明 许韵 冯玲[2] HU Ying;CHEN Xingjuan;WU Yiru;CHENG Xiaozhen;LI Siming;XU Yun;FENG Ling(Beijing University of Chinese Medicine,Beijing 100029,China;Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]北京中医药大学,北京100029 [2]中国中医科学院广安门医院,北京100053 [3]中国中医科学院,北京100700

出　　处：《中国中医基础医学杂志》2024年第7期1167-1172,共6页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：保健专项课题(2022YB73);国家自然科学基金项目(81774128);中国中医科学院科技创新工程项目(CI2021A03001,CI2021A03008)。

摘　　要：目的 观察定颤方对交感型阵发性心房颤动(atrial fibrillation, AF)大鼠电生理和心肌细胞肾上腺素能β1受体(β1-adrenergic receptor, β1-AR)信号通路的影响,探索其“脉神同调”治疗AF的潜在机制。方法 48只SD大鼠随机分为空白组、模型组、定颤方组(10.67 g/kg)和胺碘酮组(52.89 mg/kg),每组12只,连续灌胃给药14 d。实验第12天起,除空白组,其余组大鼠每日腹腔注射异丙肾上腺素(isoprenaline, ISO)1.5 mg/kg,连续3 d。第14天时,除空白组外,其余各组大鼠均行经食道心房Burst刺激进行AF诱发,观察各组大鼠有效不应期、AF诱发率和AF持续时间。采用ELISA测定各组大鼠血清去甲肾上腺素(norepinephrine, NE)水平;Western blot和RT-qPCR检测心房肌组织中β1-AR、蛋白激酶A(protein kinase A, PKA)、L型钙通道(L-type calcium channel, Cav1.2)蛋白和m RNA表达情况。结果 与空白组比较,模型组大鼠NE,β1-AR蛋白和m RNA,PKA m RNA水平升高(P<0.01),Cav1.2蛋白和m RNA水平降低(P<0.05);与模型组比较,定颤方组和胺碘酮组大鼠AF诱发次数明显减少(P<0.01),AF持续时间显著缩短(P<0.05),β1-AR蛋白和m RNA、PKA m RNA表达显著下降(P<0.05),Cav1.2蛋白和m RNA表达显著增加(P<0.01),定颤方组大鼠血清NE水平明显减少(P<0.05)。结论 定颤方能够有效抑制AF的发生和维持,其机制与调节NE、β1-AR及钙离子通道有关,可能通过抑制交感神经活性、促进钙稳态发挥“脉神同调”治疗AF的作用。Objective To observe the effect of Dingchan formula on the electrophysiology and adrenergicβ1 receptor(β1-AR)signaling pathway in rats with sympathetic paroxysmal atrial fibrillation(AF),and to explore the underlying mechanism of Maishen Tongtiao treatment method.Methods 48 SD rats were randomly divided into control group,model group,Dingchan formula group(10.67 g/kg)and amiodarone group(52.89 mg/kg),with 12 rats in each group.Rats in each group were continuously administered by gavage for 14 days.From the 12th day of the experiment,except for the control group,all rats in the other groups were daily injected with isoprenaline(ISO)1.5 mg/kg intraperitoneally for 3 days.On the 14th day,except for the control group,all rats in other groups were subjected to transesophageal atrial burst stimulation to induce AF,and electrophysiological indexes such as effective refractory period,AF induction rate and duration were observed.The serum levels of norepinephrine(NE)were measured by ELISA,and the expression ofβ1-AR,PKA and Cav 1.2 protein and mRNA in the atrial tissues of rats in each group were detected by Western blot and RT-qPCR.Results Compared with the control group,the NE levels,β1-AR protein and mRNA levels,and PKA mRNA levels were significantly higher(P<0.01),while Cav1.2 protein and mRNA expression levels were significantly lower(P<0.05)in the model group.Compared with the model group,the frequency of AF induction was significantly less(P<0.01),the duration of AF was significantly shorter(P<0.05),the expression ofβ1-AR protein and mRNA and PKA mRNA were significantly decreased(P<0.05),while the expression of Cav1.2 protein and mRNA were significantly increased(P<0.01)in Dingchan formula group and amiodarone group.The serum NE levels of rats were significantly reduced(P<0.05)in the Dingchan formula group.Conclusion Dingchan formula can effectively inhibit the occurrence and maintenance of AF,and its mechanism is related to the regulation of NE,β1-AR and calcium channels,which may play the role of Maishen Ton

关 键 词：房颤 定颤方 脉神同调 肾上腺素能受体 经食道心房调搏 

分 类 号：R285.5[医药卫生—中药学]