线粒体DNA损伤在缺血再灌注中的研究进展

Mitochondrial DNA damage in the regulation of ischemia/reperfusion injury

重症患者中缺血再灌注(I/R)的发生常会引起多器官功能障碍,最终导致死亡。I/R损伤常见于急性肠系膜缺血、创伤、感染性休克、烧伤以及外科操作等。研究结果显示,线粒体功能与I/R损伤的发生发展存在密切的联系。线粒体虽然具有生成三磷酸腺苷(ATP)的能力并被看成细胞的"发电站",但近年来,人们逐渐意识到线粒体功能紊乱能够促进炎症、氧化应激以及诱导细胞的凋亡。其中炎症应答、氧化损伤以及凋亡在I/R损伤中发挥重要的作用。研究证明,线粒体DNA(mtDNA)损伤能够诱导线粒体功能障碍从而进一步加重I/R损伤。此外,当损伤的mtDNA释放到胞质、胞外环境或循环中,它能够激活多种模式识别受体(PRRs)以触发炎症放大。本文综述了mtDNA损伤和I/R之间的关系及其作用机制,同时推测mtDNA可能成为I/R损伤潜在的作用靶点。

Ischemia/reperfusion (I/R) in critical ill patients causes multiple organ dysfunction and eventually leads to mortality. Ischemia/reperfusion (I/R) injury is a common occurrence resulting from acute mesenteric ischemia, traumatic or septic shock, burns, and surgical procedures. Mitochondria are considered as cellular factory because of their ability to produce adenosine triphosphate (ATP). Recent studies suggest that mitochondrial dysfunction can promote inflammation, oxidative stress, and induce cell death, all of which can aggravate I/R injury. Mounting evidence showed that mitochondrial DNA (mtDNA) damage can induce mitochondrial dysfunction and induce I/R injury. Additionally, when mtDNA is released into the cytoplasm, extracellular milieu or circulation, it can activate multiple pattern-recognition receptors (PRRs) to trigger pro-inflammatory responses. We review the relationship between mtDNA damage and I/R, and speculate that mtDNA may be a potential target for I/R injury.