芪参桃红颗粒对心力衰竭小鼠心肌重构的干预作用及对自噬相关miRNA的影响  

Effect of Qishen Taohong Granule on Myocardial Remodeling in Heart Failure Mice and Autophagy-related miRNA

作　　者：靳嘉麟 刘静[3] 万洁[3] 李冬 逯金金[3] 崔晓云[3] 周鹍[3] 高群 李天力 贾文浩 武乾[4] 李岩[3] 林谦[1] JIN Jialin;LIU Jing;WAN Jie;LI Dong;LU Jinjin;CUI Xiaoyun;ZHOU Kun;GAO Qun;LI Tianli;JIA Wenhao;WU Qian;LI Yan;LIN Qian(Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700,China;Beijing University of Chinese Medicine,Beijing 100029,China;Dongfang Hospital of Beijing University of Chinese Medicine,Beijing 100078,China;Experimental Research Center,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]北京中医药大学,北京100029 [3]北京中医药大学东方医院,北京100078 [4]中国中医科学院医学实验中心,北京100700

出　　处：《世界中医药》2023年第18期2589-2596,2602,共9页World Chinese Medicine

基　　金：国家自然科学基金项目(81703902,81973622)——基于mTOR自噬信号通路、自噬相关microRNA转录调控网络探讨芪参桃红颗粒抑制心衰心肌重塑的效应机制;芪参桃红颗粒通过CaMKII-Drp1-Pink1通路调控线粒体分裂与自噬改善心衰的机制研究。

摘　　要：目的:观察芪参桃红颗粒对压力负荷心力衰竭模型小鼠不同时期胸主动脉缩窄(Transverse Aortic Constriction,TAC)术后2周、4周心肌重构的干预作用及对自噬和相关微RNA(miRNA)的影响。方法:将90只C57小鼠随机分为:模型组(M组)、芪参桃红颗粒组(后简称QSTH,T组)、QSTH+雷帕霉素组(TR组)、QSTH+3-甲基腺嘌呤组(T3M组)、依那普利组(E组),假手术组(S组)。于术后2周、4周,监测心功能,行苏木精-伊红(HE)染色、Masson染色、凋亡检测并定量分析,于透射电镜下观察左室组织自噬体形成情况,并对S组、M组、T组左室组织行miRNA测序并验证。结果:术后2周时,T组在提高左心射血分数方面优于其他组(P<0.05),术后4周时,T组、E组在提高左室心射血分数方面优于其他组;除S组,其他组可见不同程度心脏几何形状变形、心肌肥厚。T组和E组相比较其他组,心肌纤维凋亡百分比更低(P<0.05)。除S组,其他组可见自噬滤泡、自噬体及自噬溶酶体,肌纤维细胞排列紊乱。M组相较于S组,测序结果提示新陈代谢通路、溶酶体通路与心肌自噬的联系非常密切并且其富集因子较高,具有显著的差异性;在T组较M组中,哺乳动物雷帕霉素靶蛋白(mTOR)、溶酶体通路富集明显,与自噬密切相关。结论:QSTH有效改善由压力负荷导致的心力衰竭小鼠的心功能及其心肌重构,其作用机制可能是基于miRNA调节自噬通量以产生相应的保护作用。Objective:To observe the intervention effect of Qishen Taohong Granule(QSTH)on myocardial remodeling in stress-loaded heart failure mice at different stages[2 weeks and 4 weeks after transverse aortic constriction(TAC)]and the effect on autophagy-related miRNA.Methods:A total of 90 C57 mice were randomly divided into model group(M group),QSTH group(T group),QSTH+rapamycin group(TR group),QSTH+3-methyladenine group(T3M group),enalapril group(E group),and sham operation group(S group).Two and four weeks after operation,cardiac function was monitored.Hematoxylin and eosin(HE)staining,Masson staining,apoptosis detection and quantitative analysis were performed,and the formation of autophagosomes in left ventricular tissues was observed under transmission electron microscopy.The miRNA sequencing and verification were performed for the left ventricular tissues in the S,M and T groups.Results:At 2 weeks after operation,T group was superior to the other groups in improving left ventricular ejection fractions(LVEF)(P<0.05),and at 4 weeks after operation,T group and E group were superior to the other groups in improving LVEF.Except S group,the geometric deformation of the heart and cardiac hypertrophy were observed in the other groups.The myocardial fiber apoptosis in T group and E group was lower than that in the other groups(P<0.05).Except S group,there were autolyfollicles,autophagosomes and autolysosomes in other groups,and myofibrocytes were arranged disorderly.Compared with that of S group,the sequencing of M group indicated that metabolic pathways and lysosomal pathways were closely related to cardiac autophagy and their enrichment factors were higher,showing a significant difference.Compared with the conditions in M group,mammalian target of rapamycin(mTOR)and lysosomal pathways in T group were enriched significantly,which were closely related to autophagy.Conclusion:QSTH improves the myocardial remodeling in stress-loaded heart failure mice,and the mechanism may be miRNA regulating autophagic flux to produce the p

关 键 词：芪参桃红颗粒 心肌重构 心力衰竭 胸主动脉缩窄 自噬 MIRNA 基因测序 

分 类 号：R289[医药卫生—方剂学]