Baoyuan decoction alleviates myocardial infarction through the regulation of metabolic dysfunction and the mitochondria-dependent caspase-9/3 pathway  

保元汤通过调节代谢紊乱和线粒体依赖的Caspase-9/3途径减轻心肌梗死

作　　者：Zhiyong Du Zeliu Shu Chun Li Xiaomin Song Xiaoli Ma Lixi Liao Jun Li Pengfei Tu Kewu Zeng Yong Jiang 杜智勇;舒泽柳;李春;宋小敏;马晓丽;廖理曦;李军;屠鹏飞;曾克武;姜勇(天然药物与仿生药物国家重点实验室,北京大学药学院,北京100191;北京中医药大学中医药现代研究中心,北京100029)

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing,China [2]Modern Research Center for Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing,China

出　　处：《Acupuncture and Herbal Medicine》2021年第1期49-58,共10页针灸和草药（英文）

基　　金：financially supported by the National Natural Sciences Foundation of China(Nos.81530097 and 81222051);the National Key Technology R&D Program“New Drug Innovation”of China(No.2017ZX09101003-008-003).

摘　　要：Objective:Baoyuan decoction(BYD)is a traditional Chinese formula with myocardial protection efficacy validated by modern pharmacological tests.The present study aimed to investigate the effect and mechanism of BYD on alleviating myocardial infarction(MI).Methods:Nuclear magnetic resonance-based serum and urinary metabolomics were employed to explore the metabolic regulation effects of BYD in rats with MI induced by left anterior descending ligation.Oxygen-glucose deprivation/recovery(OGD/R)model in H9c2 cells and multiple molecular biology approaches were used to clarify the underlying action mechanisms of BYD.Results:BYD treatment recovered the serum and urinary metabolite profiles of the MI rats toward normal metabolic status and significantly improved mitochondrial energy metabolism and apoptosis pathways perturbed by MI.Analysis of the molecular mechanism of BYD indicated that it suppressed OGD/R-induced H9c2 cell apoptosis in a concentration-dependent manner by inhibiting the mitochondria-dependent caspase-9/3-poly ADP-ribose polymerase pathway.Conclusions:Our results demonstrate that BYD protects against myocardial apoptosis via the mitochondrial metabolic and apoptosis pathways.They also provide novel insights into the clinical application of BYD for the treatment of ischemic heart diseases.目的:探究保元汤(BYD)减轻心肌梗死的作用机制。方法:采用核磁共振(NMR)代谢组学技术,观察BYD对冠脉左前降支结扎心肌梗死(MI)模型大鼠的代谢调控作用。采用H9c2细胞氧糖剥夺/恢复(OGD/R)模型和多种分子生物学方法,探究保元汤的心肌保护作用机制。结果:BYD治疗可明显改善MI大鼠血清和尿液代谢紊乱,尤其对线粒体能量代谢和凋亡途径相关的代谢小分子和通路的改善作用显著。体外心肌细胞模型及分子生物学研究结果表明,BYD呈浓度依赖性地抑制OGD/R诱导的H9c2细胞凋亡,其作用机制主要与抑制线粒体依赖的Caspase-9/3-poly-ADP核糖聚合酶(PARP)途径有关。结论:研究结果表明,BYD可以通过调控线粒体代谢、凋亡途径保护心肌细胞。本研究为BYD治疗缺血性心脏病的临床应用提供了新的见解。

关 键 词：Baoyuan decoction Caspase-9/3 pathway Mechanisms Metabolomics Mitochondrial energy metabolism Myocardial infarction 

分 类 号：R285.5[医药卫生—中药学]