Mitochondria, Oxidative Stress and Muscular Protection Laboratory (UR 3072), Biomedicine Research Centre of Strasbourg CRBS, Strasbourg, France.
Institut de Cancérologie Strasbourg Europe (ICANS), Strasbourg, France.
Am J Physiol Cell Physiol. 2024 Feb 1;326(2):C449-C456. doi: 10.1152/ajpcell.00639.2023. Epub 2023 Dec 25.
Ischemia-reperfusion (IR) is known to induce severe tissue damage, notably through mitochondrial dysfunction. Mitochondrial transplantation has emerged as a promising therapeutic strategy in cardiac IR; however, few studies have previously assessed its efficacy in the context of peripheral IR. Therefore, the objective of this study was to assess the effect of mitochondrial transplantation in a hindlimb model of IR injury. Thirty-six SWISS mice were divided into three groups: control (CTL, = 12), ischemia-reperfusion (IR, = 12), and IR with mitochondrial transplantation (MT, = 12). Ischemia (2 h) was induced using the tourniquet model around the right hind limb in the IR and MT groups. In MT group, mitochondria isolated from the right rectus muscle, a nonischemic region, were injected shortly before reperfusion. Mitochondrial respiration, calcium retention capacity, and Western blotting analysis were performed 2 h after reperfusion. Compared with the CTL group, IR led to a decrease in the mitochondrial respiratory capacity, particularly for the basal state (-30%; = 0.015), oxidative phosphorylation (-36%; = 0.024), and calcium retention capacity (-45%; = 0.007). Interestingly, mitochondrial transplantation partially restored these functions since no differences between MT and CTL groups were found. In addition, the administration of healthy mitochondria resulted in a positive regulation of redox balance and mitochondrial dynamics within the skeletal muscle. Although further investigations are needed to better characterize underlying mechanisms, mitochondrial transplantation represents a promising strategy in the setting of IR-induced muscular damage. Ischemia-reperfusion injury leads to severe muscular damage. Even if prompt revascularization is the treatment of choice, muscular alterations can lead to severe sequalae as mitochondrial dysfunction. Accordingly, adjunctive strategies are needed to overcome the muscular damage. Mitochondrial transplantation has shown beneficial effects in cardiac ischemia-reperfusion, but its role in peripheral muscle is not well established. In this study, we found that mitochondrial transplantation partially restored muscular function when submitted to ischemia reperfusion.
缺血再灌注（IR）已知会引起严重的组织损伤，特别是通过线粒体功能障碍。线粒体移植已成为心脏 IR 治疗的一种有前途的策略；然而，以前很少有研究评估其在外周 IR 情况下的疗效。因此，本研究的目的是评估线粒体移植在缺血后肢模型中的效果。36 只瑞士小鼠分为三组：对照组（CTL，n=12）、缺血再灌注组（IR，n=12）和线粒体移植组（MT，n=12）。IR 和 MT 组通过在右后肢周围使用止血带模型诱导缺血（2 小时）。在 MT 组中，在再灌注前不久将从非缺血区域右直肌中分离出的线粒体注射。在再灌注后 2 小时进行线粒体呼吸、钙保留能力和 Western blot 分析。与 CTL 组相比，IR 导致线粒体呼吸能力下降，特别是基础状态下（-30%；p=0.015）、氧化磷酸化（-36%；p=0.024）和钙保留能力（-45%；p=0.007）。有趣的是，线粒体移植部分恢复了这些功能，因为 MT 和 CTL 组之间没有差异。此外，给予健康的线粒体导致骨骼肌内氧化还原平衡和线粒体动力学的正向调节。尽管需要进一步研究来更好地描述潜在机制，但线粒体移植在外周 IR 诱导的肌肉损伤中代表了一种有前途的策略。缺血再灌注损伤导致严重的肌肉损伤。即使及时再血管化是首选治疗方法，肌肉改变也会导致严重的后遗症，如线粒体功能障碍。因此，需要辅助策略来克服肌肉损伤。线粒体移植在心脏缺血再灌注中显示出有益的效果，但在外周肌肉中的作用尚未得到充分确立。在这项研究中，我们发现线粒体移植在经历缺血再灌注时部分恢复了肌肉功能。
