Kidneys from deceased donors used for transplantation are placed in cold storage (CS) solution during the search for a matched recipient. However, CS induces mitochondrial and cellular injury, which exacerbates renal graft dysfunction, highlighting the need for therapeutic interventions. Using an in vitro model of renal CS, we recently reported that pharmacological activation of the mitochondrial BK channel (mitoBK) during CS protected against CS-induced mitochondrial injury and cell death. Here, we used an in vivo syngeneic rat model of renal CS (18 h) followed by transplantation (24 h reperfusion) (CS + Tx) to similarly evaluate whether addition of a mitoBK activator to the CS solution can alleviate CS + Tx-induced renal injury. Western blots detected the pore-forming α subunit of the BK channel in mitochondrial fractions from rat kidneys, and mitoBK protein level was reduced after CS + Tx compared to sham surgery. The addition of the BK activator NS11021 (3 μM) to the CS solution partially protected against CS + Tx-induced mitochondrial respiratory dysfunction, oxidative protein nitration, and cell death, but not acute renal dysfunction (SCr and BUN). In summary, the current preclinical study shows that pharmacologically targeting mitoBK channels during CS may be a promising therapeutic intervention to prevent CS + Tx-induced mitochondrial and renal injury.

在寻找匹配的受者期间，用于移植的已故捐赠者的肾脏被放置在冷藏 (CS) 溶液中。然而，CS 诱导线粒体和细胞损伤，从而加剧肾移植功能障碍，突出了治疗干预的必要性。使用肾 CS 的体外模型，我们最近报道了 CS 期间线粒体 BK 通道 (mitoBK) 的药理学激活可以防止 CS 诱导的线粒体损伤和细胞死亡。在这里，我们使用了体内肾 CS（18 小时）的同基因大鼠模型，然后进行移植（24 小时再灌注）（CS + Tx），以类似地评估将 mitoBK 激活剂添加到 CS 溶液中是否可以减轻 CS + Tx 诱导的肾损伤。蛋白质印迹检测到大鼠肾脏线粒体部分中 BK 通道的成孔 α 亚基，与假手术相比，CS + Tx 后 mitoBK 蛋白水平降低。在 CS 溶液中添加 BK 激活剂 NS11021 (3 μM) 可以部分防止 CS + Tx 诱导的线粒体呼吸功能障碍、氧化蛋白硝化和细胞死亡，但不能防止急性肾功能障碍（SCr 和 BUN）。总之，