Su Xin, Zhou Mingyang, Li Yingjian, Zhang Jianzhen, An Na, Yang Fan, Zhang Guoxia, Yuan Chao, Chen Hengwen, Wu Hongjin, Xing Yanwei
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Biomed Pharmacother. 2022 May;149:112893. doi: 10.1016/j.biopha.2022.112893. Epub 2022 Mar 31.
Patients with ischemic heart disease receiving reperfusion therapy still need to face left ventricular remodeling and heart failure after myocardial infarction. Reperfusion itself paradoxically leads to further cardiomyocyte death and systolic dysfunction. Ischemia/reperfusion (I/R) injury can eliminate the benefits of reperfusion therapy in patients and causes secondary myocardial injury. Mitochondrial dysfunction and structural disorder are the basic driving force of I/R injury. We summarized the basic relationship and potential mechanisms of mitochondrial injury in the development of I/R injury. Subsequently, this review summarized the natural products (NPs) that have been proven to targeting mitochondrial therapeutic effects during I/R injury in recent years and related cellular signal transduction pathways. We found that these NPs mainly protected the structural integrity of mitochondria and improve dysfunction, such as reducing mitochondrial division and fusion abnormalities, improving mitochondrial Ca overload and inhibiting reactive oxygen species overproduction, thereby playing a role in protecting cardiomyocytes during I/R injury. This data would deepen the understanding of I/R-induced mitochondrial pathological process and suggested that NPs are expected to be transformed into potential therapies targeting mitochondria.
接受再灌注治疗的缺血性心脏病患者在心肌梗死后仍需面对左心室重构和心力衰竭。矛盾的是,再灌注本身会导致进一步的心肌细胞死亡和收缩功能障碍。缺血/再灌注(I/R)损伤会消除再灌注治疗对患者的益处,并导致继发性心肌损伤。线粒体功能障碍和结构紊乱是I/R损伤的基本驱动力。我们总结了I/R损伤发生过程中线粒体损伤的基本关系和潜在机制。随后,本综述总结了近年来已被证明在I/R损伤期间具有靶向线粒体治疗作用的天然产物(NPs)以及相关的细胞信号转导途径。我们发现,这些NPs主要保护线粒体的结构完整性并改善功能障碍,例如减少线粒体分裂和融合异常、改善线粒体钙超载以及抑制活性氧过度产生,从而在I/R损伤期间对心肌细胞起到保护作用。这些数据将加深对I/R诱导的线粒体病理过程的理解,并表明NPs有望转化为靶向线粒体的潜在治疗方法。