摘要
目的 探讨抗纤益心方治疗扩张型心肌病(DCM)的可能作用机制。方法 30只cTnTR141W转基因DCM小鼠随机分为模型组、抗纤益心颗粒组、辅酶Q10组,每组10只,另设10只C57BL/6J小鼠为正常组。辅酶Q10组、抗纤益心颗粒组分别给予辅酶Q10片1.5 mg/(kg·d)、抗纤益心方配方颗粒20.4 g/(kg·d)灌胃,正常组、模型组给予生理盐水7.5 ml/(kg·d)灌胃。干预8周后检测各组小鼠心功能[包括左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)、左室轴缩短率(FS)],观察心肌组织病理学形态及心肌超微结构,检测心肌组织三磷酸腺苷(ATP)和磷酸肌酸(PCr)含量,线粒体质量控制相关蛋白Drp1、Mff、Mfn1、Opa1、Pink1、Parkin、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)表达水平。结果 与正常组比较,模型组LVEDD、LVESD增大,LVEF、FS降低(P<0.05);心肌细胞排列紊乱,纤维化明显,心脏超微结构损伤明显;PCr含量、PCr/ATP值降低(P<0.05),Drp1、Mff、Pink1、Parkin及PGC-1α蛋白表达均减少(P<0.05)。与模型组比较,抗纤益心颗粒组、辅酶Q10组LVEDD、LVESD降低,LVEF升高(P<0.05);抗纤益心颗粒组、辅酶Q10组心肌细胞形态均有所改善,病理纤维化程度减轻,心脏超微结构损伤减轻;抗纤益心颗粒组PCr含量、PCr/ATP值升高,Mff、Pink1、Parkin、PGC-1α蛋白表达增加(P<0.05),辅酶Q10组Pink1、PGC-1α蛋白表达增加(P<0.05)。与抗纤益心颗粒组比较,辅酶Q10组Parkin蛋白表达下降(P<0.05)。结论 抗纤益心方能有效改善DCM小鼠心功能,其机制可能与调控心肌组织线粒体质量控制有关。
Objective To explore the possible mechanism of Kangxian Yixin Formula(抗纤益心方,KYF)in the treatment of dilated cardiomyopathy(DCM).Methods Thirty c Tn TR141Wtransgenic mice with DCM were randomly divided into the model group,KYF group and coenzyme Q10 group,with 10 mice in each group.Ten C57BL/6J mice were set as the normal group.Coenzyme Q10 solution at a dose of 1.5 mg/(kg·d),and KYF at a dose of 20.4 g/(kg·d)were given by gavage to the corresponding coenzyme Q10 group and KYF group,respectively.For the normal group and the model group,normal saline at a dose of 10 ml/(kg·d)were given by gavage.After eight weeks intervention,the cardiac function indicators including left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(FS)were assessed.The myocardial histopathology and ultrastructure were observed.The levels of adenosine triphosphate(ATP)and creatine phosphate(PCr),as well as the expression levels of mitochondrial quality control-related proteins including Drp1,Mff,Mfn1,Opa1,Pink1,Parkin,and peroxisome proliferator-activated receptor gamma coactivator 1α(PGC-1α)were detected.Results Compared to the normal group,the model group had significantly increased LVEDD and LVESD,as well as reduced EF and FS(P<0.05).Moreover,in the model group,there were disordered cardiomyocytes,significant fibrosis and damaged ultrastructure;the PCr level and the PCr/ATP ratio significantly decreased(P<0.05),and the expressions of Drp1,Mff,Pink1,Parkin and PGC-1αwere reduced(P<0.05).Compared to those in the model group,LVEDD and LVESD in the KYF group and the coenzyme Q10 group significantly decreased,while LVEF significantly increased(P<0.05);the morphology of myocardial cells was improved,and the pathological fibrosis and the cardiac ultrastructural damage were reduced.Moreover,in the KYF group,PCr level and PCr/ATP ratio,as well as expression of Mff,Pink1,Parkin,and PGC-1αsignificantly increased(P<0.05);in the coenzyme Q10 group,the expression of Pink1 and PGC-1αsignificantly increased(P<0.05).Compared to the KYF group,the coenzyme Q10 group had significantly lower expression of Parkin(P<0.05).Conclusion KYF can effectively improve the cardiac function of mice with DCM,the mechanism may be related to the regulation of mitochondrial quality control.
作者
王冰
刘舜禹
王振涛
冯尧伟
常红波
黑炫鼎
吴鸿
WANG Bing;LIU Shunyu;WANG Zhentao;FENG Yaowei;CHANG Hongbo;HEI Xuanding;WU Hong(The Second Clinical Medical College of Henan University of Chinese Medicine,Zhengzhou,450046;Henan Provincial Hospital of Traditional Chinese Medicine)
出处
《中医杂志》
CSCD
北大核心
2022年第7期664-670,共7页
Journal of Traditional Chinese Medicine
基金
河南省科技攻关项目(212102310368)
河南省中医药科学研究专项(20-21ZY2009)。
关键词
扩张型心肌病
线粒体质量控制
抗纤益心方
心功能
能量代谢
dilated cardiomyopathy
mitochondrial quality control
Kangxian Yixin Formula(抗纤益心方)
cardiac function
energy metabolisml
