BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and...BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.展开更多
目的:探讨针刺“内关”穴对缓慢性心律失常的调节机制。方法:用异搏定诱发大鼠心律失常模型,成功后电针双侧“内关”穴。用美国B IOPAC System s MP150生物信号采集系统记录心电图,观察针刺前后心律(率)变化;用半定量逆转录聚合酶链反应...目的:探讨针刺“内关”穴对缓慢性心律失常的调节机制。方法:用异搏定诱发大鼠心律失常模型,成功后电针双侧“内关”穴。用美国B IOPAC System s MP150生物信号采集系统记录心电图,观察针刺前后心律(率)变化;用半定量逆转录聚合酶链反应(RT-PCR)方法测定心肌中GsmRNA的相对含量。结果:针刺治疗组与模型组相比有显著变化。结论:缓慢性心律失常可能和G蛋白信号转导障碍有关,G蛋白在针刺“内关”穴对心律失常的调节中有重要作用。展开更多
基金supported by a grant from Surface Project of Natural Science Foundation of Fujian Province(2008J0075)
文摘BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.
文摘目的:基于网络药理学探讨养心定悸胶囊治疗室性心律失常(Ventricular Arrythmia,VA)的作用机制。方法:使用中药系统药理学数据库与分析平台(TCMSP)和BATMAN-TCM等数据库筛选养心定悸胶囊的有效成分及其作用靶点,通过GeneCards、OMIM等数据库检索VA的疾病靶点,制作韦恩图,获得相关交集。使用STRING数据库制作靶点间相互作用网络,筛选关键靶点及关键成分,使用Cytoscape 3.9.1软件构建成分-靶点-通路网络。运用DAVID网站进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。结果:检索到活性成分146种,预测靶点761个,疾病靶点2 126个,交集靶点222个。构建的网络最终获得47个节点和708条边,获得10个核心靶点,包括重组人信号转导与转录激活因子3(Signal Transducer and Activator of Transcription 3,STAT3)、丝氨酸/苏氨酸蛋白激酶1(Serine-Threonine Protein Kinase 1,AKT1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等。GO和KEGG富集分析与筛选显示,养心定悸胶囊治疗VA的作用通路包括磷代谢过程的正调控、细胞运动的正调控、对外源性刺激的反应等。结论:养心定悸胶囊治疗VA通过多成分、多靶点作用于磷代谢过程的正调控、对激素的反应、细胞运动的正调控等多通路发挥药效。
文摘目的:探讨针刺“内关”穴对缓慢性心律失常的调节机制。方法:用异搏定诱发大鼠心律失常模型,成功后电针双侧“内关”穴。用美国B IOPAC System s MP150生物信号采集系统记录心电图,观察针刺前后心律(率)变化;用半定量逆转录聚合酶链反应(RT-PCR)方法测定心肌中GsmRNA的相对含量。结果:针刺治疗组与模型组相比有显著变化。结论:缓慢性心律失常可能和G蛋白信号转导障碍有关,G蛋白在针刺“内关”穴对心律失常的调节中有重要作用。
