丹七片对缺血性心脏病大鼠模型能量代谢的调节作用  

Regulatory Effect of Danqi Tablet on Energy Metabolism in a Rat Model of Ischemic Heart Disease

作　　者：刘慧 刘静 刘聪 党晶艺 王海燕 LIU Hui;LIU Jing;LIU Cong;DANG Jingyi;WANG Haiyan(Department of Cardiology,the Second Affiliated Hospital,Air Force Medical University of People′s Liberation Army of China,Xi′an 710032,China)

机构地区：[1]解放军空军军医大学第二附属医院心内科,西安710032

出　　处：《世界中医药》2021年第15期2322-2327,共6页World Chinese Medicine

基　　金：陕西省重点研发计划项目(2018YBXM-SF-12-1);唐都医院创新发展基金资助项目(2018QYTS011)。

摘　　要：目的:探讨丹七片对缺血性心脏病大鼠模型能量代谢的调节作用。方法:通过结扎左前降支冠状动脉建立缺血性心脏大鼠模型,将48只大鼠分为假手术组、模型组、丹七片组和曲美他嗪组,每组12只。丹七片组大鼠以500.0 mg/kg的剂量灌胃丹七片溶液,曲美他嗪组大鼠以6.0 mg/kg的剂量灌胃曲美他嗪溶液,其他组大鼠灌胃生理盐水。治疗1个月后评价各组大鼠的心脏功能、心肌组织和细胞病理改变、心肌ATP水平及AMPK/SIRT1/PGC-1α信号通路及其下游分子表达水平。结果:超声心动图显示,与模型组比较,丹七片组大鼠的LVIDs和LVIDd分别减少了26.35%和20.73%,而EF和FS分别增加了31.61%和42.82%,差异有统计学意义(P<0.05)。HE染色结果显示,丹七片组的心肌细胞排列较为整齐,细胞水肿减轻,细胞间隙减小,炎性细胞减少。与模型组比较,丹七片组大鼠的心肌ATP水平显著增加(P<0.05)。免疫组织化学染色结果显示,与模型组比较,丹七片组大鼠PGC-1α的阳性染色评分显著升高(P<0.05)。Western Blotting结果显示,与模型组比较,丹七片组大鼠的AMPK、SIRT1、PGC-1α、MFN1、MFN2和SOD2蛋白表达均显著升高(P<0.05)。结论:丹七片可以在缺血性心脏病大鼠模型中发挥心脏保护功能,并上调ATP的产生。丹七片可激活AMPK/SIRT1/PGC-1α信号通路及其下游分子,改善能量代谢并还调节线粒体的生物合成,从而改善大鼠心脏功能并防止心肌损伤。Objective:To investigate the regulation of energy metabolism with Danqi Tablet in a rat model of ischemic heart disease.Methods:A rat model of ischemic heart was established by ligation of the left anterior descending coronary artery.A total of 48 rats were divided into a sham an operation group,a Danqi tablet group and trimetazidine group,with 12 rats in each group.Rats in the Danqi Tablets were given a solution of Danqi Tablets at a dose of 500.0 mg/kg.Rats in the trimetazidine group were given a solution of trimetazidine at a dose of 6.0 mg/kg.The other groups were given normal saline.After 1 month of treatment,cardiac function,myocardial tissue cytopathological changes,myocardial ATP levels,and AMPK/SIRT1/PGC-1αsignaling pathway and downstream molecular expression were evaluated.Results:Echocardiography showed that compared with the model group,LVIDs and LVIDd in the Danqi tablet group were reduced by 26.35%and 20.73%,while EF and FS increased by 31.61%and 42.82%,and the difference was significant(P<0.05).The results of HE staining showed that the cardiomyocytes in the Danqi tablet group were arranged neatly,the cell edema was reduced,the cell gap was reduced,and the inflammatory cells were decreased.Compared with the model group,the myocardial ATP level of the Danqi tablet group increased significantly(P<0.05).Immunohistochemical staining showed that the PGC-1αpositive staining score of rats in the Danqipian group was significantly higher than that of the model group(P<0.05).Western Blotting showed that the expression levels of AMPK,SIRT1,PGC-1α,MFN1,MFN2 and SOD2 were significantly increased in the Danqi Tablets group compared with the model group(P<0.05).Conclusion:Danqi Tablet can play a cardioprotective function in the rat model of ischemic heart disease and up-regulate ATP production.Danqi Tablets activate the AMPK/SIRT1/PGC-1αsignaling pathway and its downstream molecules,improve energy metabolism and also regulate mitochondrial biogenesis,thereby improving rat cardiac function and preventing myoca

关 键 词：丹七片 缺血性心脏病 能量代谢 线粒体 心肌损伤 三磷酸腺苷 AMPK/SIRT1/PGC-1α信号通路 

分 类 号：R289.5[医药卫生—方剂学] R542[医药卫生—中药学]