抗纤益心方对扩张型心肌病大鼠心肌细胞PKA/CaMKⅡ信号通路及线粒体膜电位的影响  

Effect of Kangxian Yixin Decoction on PKA/CaMKⅡSignal Pathway and Mitochondrial membrane potential of Cardiomyocyte in Rats with Dilated Cardiomyopathy

作　　者：曾垂义[1] 王振涛[1] 黑炫鼎 王冰[1] 常红波[1] ZENG Chuiyi;WANG Zhentao;HEI Xuanding;WANG Bing;CHANG Hongbo(Henan Province Hospital of TCMHenan University of Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学河南省中医院,郑州450000

出　　处：《世界科学技术-中医药现代化》2024年第6期1601-1607,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家中医临床研究基地科研专项课题(2019JDZX015):不同益气剂量抗纤益心方对扩张型心肌病大鼠心功能的影响,负责人:曾垂义;河南省中医药拔尖人才培养项目(豫卫中医函[2021]15号):抗纤益心方对扩张型心肌病心肌能量代谢的影响,负责人:曾垂义;河南省特色骨干学科中医学学科建设项目(STG-ZYXKY-2020013):大气下陷理论治疗心血管疾病的文献挖掘整理及在扩张型心肌病中的应用研究,负责人:曾垂义。

摘　　要：目的通过抗纤益心方干预扩张型心肌病大鼠,探讨该药在扩张型心肌病心肌细胞PKA/CaMKⅡ信号通路及线粒体膜电位方面的作用。方法扩张型心肌病大鼠通过饮用呋喃唑酮复制,连续10周后通过心脏彩超确定模型复制成功,随机分为抗纤益心方低剂量组、抗纤益心方中剂量组、抗纤益心方高剂量组、卡托普利组和模型组,另设正常组。药物干预4周后观察各组大鼠心肌细胞超微结构;心肌细胞ATP、Ca^(2+)-Mg^(2+)-ATP酶活力;心肌细胞CaMKⅡ、PKA、UCP2 mRNA表达。用去甲肾上腺素诱导H9c2心肌细胞肥大模型,药物干预24 h后检测心肌细胞线粒体膜电位水平。结果与正常组相比,各模型组大鼠心肌细胞线粒体受损,心肌细胞ATP、Ca^(2+)-Mg^(2+)-ATP酶活力明显降低,UCP2 mRNA、CaMKⅡmRNA均明显升高,PKA mRNA明显降低,心肌线粒体膜电位水平明显下降(P<0.05或P<0.01)。各药物干预组对心肌细胞线粒体有不同程度的保护作用,对所测指标有不同程度的改善,尤其以抗纤益心方高剂量组更为明显(P<0.05或P<0.01)。结论抗纤益心方可以减轻DCM模型大鼠心肌细胞线粒体损伤,改善心肌细胞能量代谢及舒缩功能,改善心肌细胞PKA/CaMKⅡ信号通路及线粒体膜电位水平是其机制之一。Objective To explore the effect of Kangxian Yixin decoction on PKA/CaMKⅡSignal Pathway and Mitochondrial membrane potential of cardiomyocyte hypertrophy in dilated cardiomyopathy rats.Methods Drinking furazolidone to duplicate the DCM rats model for 10 weeks,then the rats were checked by ultrasound,the successfully established model rats were randomly divided into model group,low dose Kangxian Yixin decoction group,middle dose Kangxian Yixin decoction group,high dose Kangxian Yixin decoction group and captopril group.Normal group was separated.After 4 weeks of drug intervention,This experiment was over,ATP,Ca^(2+)-Mg^(2+)-ATP enzymatic activity,CaMKⅡ,PKA and UCP2 mRNA were tested.H9c2 cardiomyocyte hypertrophy model was set up by norepinephrine,after 24 h of drug intervention,mitochondrial membrane potential was tested.Results Compared with the normal group,cardiomyocyte mitochondria were damaged in each model group,ATP,Ca^(2+)-Mg^(2+)-ATP enzymatic activity and PKA mRNA were lower,UCP2 mRNA and CaMKⅡmRNA were higer,mitochondrial membrane potential obviously decreased(P<0.05 or P<0.01).The mitochondria were protected in every drug group,the tested indexes get well in different degree,especially in hige dose Kangxian Yixin decoction group(P<0.05 or P<0.01).Conclusion Kangxian Yixin decoction can reduce myocardial cell mitochondrial damage in model rats with DCM,improve myocardial cell energy metabolism and cardiac systolic and diastolic functions,one of the mechanisms may be optimizing PKA/CaMKⅡsignal pathway and improving mitochondrial membrane potential.

关 键 词：扩张型心肌病 抗纤益心方 PKA/CaMKⅡ信号通路 线粒体膜电位 

分 类 号：R285.5[医药卫生—中药学]