Department of Exercise and Sports Physiology, Hacettepe University, Ankara, Turkey; Department of Pathology, Gulhane Training and Research Hospital, Health Sciences University, Ankara, Turkey.
Department of Physiology, Hacettepe University, Ankara, Turkey.
Toxicol Appl Pharmacol. 2021 Dec 15;433:115780. doi: 10.1016/j.taap.2021.115780. Epub 2021 Oct 29.
Ischemia/Reperfusion (I/R) injury is clinically important in many surgical practice including kidney transplantation. It is known that mitochondria have a key role in the intracellular and extracellular signaling pathways of ischemia and reperfusion injury. In this respect, we pointed to explore the probable effects of isolated mitochondria transplantation from MSCs (mesenchymal stem cells), to alleviate ischemia/reperfusion-induced renal injury. Experiments were held on the 48 male Sprague Dawley rats. Groups were divided as Control (C1), I/R-Control (C2), Vehicle-1 (V1), Vehicle-2 (V2), Transplantation-1 (T1) and Transplantation-2 (T2) group. Unilaterally nephrectomy was performed in all groups. In the groups except the control, the left kidneys ischemized for 45 min and then reperfusion was carried out. According to the study groups, isolated mitochondria or vehicle infused into the renal cortex and rats were monitored for 48 h. Following that mentioned procedure, animals were sacrificed and biological samples were taken for physiological, histological and biochemical examinations. The results of present study show that mitochondrial transplantation promoted proliferation and regeneration of tubular cells after renal injury. Moreover, mitochondrial transplantation reduced mitochondrial dynamics-DRP-1 fission protein of tubular cells and reversed renal deficits. Mitochondrial transplantation diminished apoptotic markers including TUNEL and Caspase-3 levels in injured renal cells. Our results provide a direct link between mitochondria dysfunction and ischemia/reperfusion-induced renal injury and suggest a therapeutic effect of transplanting isolated mitochondria obtained from MSCs against renal injury.
缺血/再灌注（I / R）损伤在包括肾移植在内的许多外科手术中具有重要的临床意义。已知线粒体在缺血和再灌注损伤的细胞内和细胞外信号通路中具有关键作用。在这方面，我们指出探讨从间充质干细胞（MSC）中分离出的线粒体移植的可能作用，以减轻缺血/再灌注引起的肾损伤。实验在 48 只雄性 Sprague Dawley 大鼠上进行。将这些动物分为对照组（C1）、缺血/再灌注对照组（C2）、载体 1 组（V1）、载体 2 组（V2）、移植 1 组（T1）和移植 2 组（T2）。所有组都进行了单侧肾切除术。在除对照组之外的所有组中，左肾缺血 45 分钟，然后再灌注。根据研究组的不同，将分离的线粒体或载体注入肾皮质，然后监测大鼠 48 小时。进行上述操作后，处死动物并采集生物样本进行生理、组织学和生化检查。本研究的结果表明，线粒体移植促进了肾损伤后肾小管细胞的增殖和再生。此外，线粒体移植减少了肾小管细胞的线粒体动力学-DRP-1 裂变蛋白，并逆转了肾损伤。线粒体移植减少了损伤肾细胞中的凋亡标志物，包括 TUNEL 和 Caspase-3 水平。我们的结果提供了线粒体功能障碍与缺血/再灌注引起的肾损伤之间的直接联系，并表明从 MSC 中分离出的分离线粒体移植对肾损伤具有治疗作用。
