德巴金通过上调自噬减轻心肌缺血再灌注损伤。
Dexpramipexole attenuates myocardial ischemia/reperfusion injury through upregulation of mitophagy.
机构信息
Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Gongye Road, Guangzhou, 510280, China; Department of Cardiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450000, China.
出版信息
Eur J Pharmacol. 2021 May 15;899:173962. doi: 10.1016/j.ejphar.2021.173962. Epub 2021 Feb 19.
Reperfusion causes undesirable damage to the ischemic myocardium while restoring the blood flow. In this study, we evaluated the effects of dexpramipexole (DPX) on myocardial injury induced by ischemia/reperfusion (I/R) in-vivo and the hypoxia/reoxygenation (HR) in-vitro and examined the functional mechanisms of DPX. DPX protected cells against H/R-induced mitochondrial dysfunction and prevented H/R damage. Both myocardial infarct size and tissue damage due to I/R was reduced upon DPX treatment. We discovered that DPX enhanced mitophagy in-vivo and in-vitro, which was accompanied by enhanced expression of PINK1 and Parkin. Knock-down of PINK1 and Parkin by specific siRNAs reversed DPX-induced inhibition of myocardial I/R injury. These findings suggest that DPX might protect against myocardial injury via PINK1 and Parkin.
再灌注在恢复血流的同时对缺血性心肌造成不良损伤。在这项研究中，我们评估了右苯丙哌林（DPX）对体内缺血/再灌注（I/R）和体外缺氧/复氧（HR）诱导的心肌损伤的影响，并研究了 DPX 的功能机制。DPX 可保护细胞免受 H/R 诱导的线粒体功能障碍，并防止 H/R 损伤。DPX 治疗可减少 I/R 引起的心肌梗死面积和组织损伤。我们发现 DPX 增强了体内和体外的线粒体自噬，同时伴随着 PINK1 和 Parkin 的表达增强。用特异性 siRNA 敲低 PINK1 和 Parkin 可逆转 DPX 诱导的心肌 I/R 损伤抑制作用。这些发现表明，DPX 可能通过 PINK1 和 Parkin 来保护心肌免受损伤。
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