Static cold storage (SCS) is the standard technique for organ preservation during transplantation, resulting in cold ischemic injury. Hypoxia can induce pannexin 1 (Panx1) channels to open, leading to release of adenosine triphosphate. However, it is unknown if Panx1 plays a role in SCS. In this study, livers from Panx1−/− mice exhibited reduced adenosine triphosphate release, resulting in hepatocyte protection during preservation. The donor liver damage was decreased during SCS when Panx1 activity was blocked. Transmission electron microscopy revealed a decrease in mitochondria-associated endoplasmic reticulum membranes and improved mitochondria morphology. Mechanistically, Panx1 blockade upregulated the phosphatidylinositol 3-kinase–protein kinase B pathway and increased B cell leukemia/lymphoma 2 levels to combat apoptosis during liver preservation. The data indicate that blocking Panx1 during preservation of the donor liver can effectively improve mitochondrial function and reduce cellular stress damage thereby decreasing cold ischemia and reperfusion-related injuries in liver transplantation.

中文翻译：

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阻断供体肝脏泛连接蛋白 1 通道有助于肝移植过程中的线粒体保护


静态冷藏 （SCS） 是移植过程中器官保存的标准技术，可导致冷缺血性损伤。缺氧可诱导泛连接蛋白 1 （Panx1） 通道打开，导致三磷酸腺苷释放。然而，目前尚不清楚 Panx1 是否在 SCS 中发挥作用。在这项研究中，Panx1 −/− 小鼠的肝脏表现出三磷酸腺苷释放减少，从而在保存过程中保护肝细胞。当 Panx1 活性被阻断时，SCS 期间供体肝损伤减少。透射电子显微镜显示线粒体相关内质网膜减少，线粒体形态改善。从机制上讲，Panx1 阻断上调磷脂酰肌醇 3-激酶-蛋白激酶 B 通路并增加 B 细胞白血病/淋巴瘤 2 水平以对抗肝脏保存过程中的细胞凋亡。数据表明，在供体肝脏保存过程中阻断 Panx1 可有效改善线粒体功能并减少细胞应激损伤，从而减少肝移植中的冷缺血和再灌注相关损伤。