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整合网络分析与实验验证以揭示益气活血(YQHX)方剂治疗心肌缺血/再灌注损伤的线粒体自噬相关机制。

Integrating network analysis and experimental validation to reveal the mitophagy-associated mechanism of Yiqi Huoxue (YQHX) prescription in the treatment of myocardial ischemia/reperfusion injury.

作者信息

Chen Mingtai, Zhong Guofu, Liu Mengnan, He Hao, Zhou Jie, Chen Jianping, Zhang Mingsheng, Liu Qiang, Tong Guangdong, Luan Jienan, Zhou Hua

机构信息

Department of Cardiovascular Disease, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, PR China; Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao.

Intensive Care Unit, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou university of Chinese Medicine, Shenzhen, PR China.

出版信息

Pharmacol Res. 2023 Mar;189:106682. doi: 10.1016/j.phrs.2023.106682. Epub 2023 Feb 1.

DOI:10.1016/j.phrs.2023.106682
PMID:36736970
Abstract

Myocardial ischemia/reperfusion (I/R) injury is the main cause of increasing postischemic heart failure and currently there is no definite treatment for myocardial I/R injury. It has been suggested that oxidative stress-induced mitochondrial dysfunction plays an important role in the pathological development of myocardial I/R. In this study, Yiqi Huoxue (YQHX) prescription, as a kind of Chinese herbal formula, was developed and shown to alleviate I/R injury. Network analysis combined with ultrahigh-performance liquid chromatography-high resolution mass spectrometry expounded the active components of YQHX and revealed the mitophagy-regulation mechanism of YQHX treating I/R injury. In vivo experiments confirmed YQHX significantly alleviated I/R myocardial injury and relieved oxidative stress. In vitro experiments validated that YQHX could relieve hypoxia/reoxygenation injury and attenuate oxidative stress via improving the structure and function of mitochondria, which was strongly related to regulating mitophagy. In summary, this study demonstrated that YQHX, which could alleviate I/R injury via targeting mitophagy, might be a potential therapeutic strategy for myocardial I/R injury.

摘要

心肌缺血/再灌注(I/R)损伤是缺血后心力衰竭增加的主要原因,目前对于心肌I/R损伤尚无确切的治疗方法。有研究表明,氧化应激诱导的线粒体功能障碍在心肌I/R的病理发展中起重要作用。在本研究中,益气活血(YQHX)方剂作为一种中药配方被研发出来,并显示出可减轻I/R损伤。网络分析结合超高效液相色谱-高分辨率质谱阐明了YQHX的活性成分,并揭示了YQHX治疗I/R损伤的线粒体自噬调节机制。体内实验证实YQHX显著减轻了I/R心肌损伤并缓解了氧化应激。体外实验验证了YQHX可通过改善线粒体的结构和功能来减轻缺氧/复氧损伤并减轻氧化应激,这与调节线粒体自噬密切相关。总之,本研究表明,YQHX可通过靶向线粒体自噬减轻I/R损伤,可能是心肌I/R损伤的一种潜在治疗策略。

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