阻断供体肝脏Pannexin 1通道有利于肝移植过程中的线粒体保护(3966)。

IF 8.9 2区 医学 Q1 SURGERY American Journal of Transplantation Pub Date : 2024-10-29 DOI:10.1016/j.ajt.2024.10.021
Shiquan Xu, Hao Li, Yuxue Gao, Yaohui Wang, Bo Zhu, He Shi, Jie Wang, Xia Wu, Ying Wang, Baojie Shi, Zhaojie Su, Yang Zhang, Zhihai Peng, Xiaoyu Yu
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引用次数: 0

摘要

静态冷藏(SCS)是移植过程中保存器官的标准技术,会造成低温缺血性损伤。缺氧可诱导 Panx1 通道开放,导致 ATP 释放。然而,Panx1 在 SCS 中是否发挥作用尚不得而知。我们的研究表明,Panx1-/-小鼠的肝脏ATP释放减少,从而在保存过程中保护了肝细胞。阻断 Panx1 可减少 SCS 期间供体肝脏的损伤。透射电子显微镜显示线粒体相关ER膜(MAMs)减少,线粒体形态改善。从机理上讲,阻断Panx1可上调PI3K-AKT通路并提高Bcl2水平,从而在保肝过程中对抗细胞凋亡。这些数据表明,在供肝保存过程中阻断Panx1能有效改善线粒体功能,减少细胞应激损伤。而冷缺血和再灌注相关损伤在肝移植中也会明显减少。
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Blocking donor liver Pannexin 1 channels facilitates mitochondria protection during liver transplantation(3966).

Static cold storage (SCS) is the standard technique for organ preservation during transplantation, resulting in cold ischemic injury. Hypoxia can induce Panx1 channels open, leading to release of ATP. However, it is unknown whether Panx1 play a role in SCS. Our research demonstrates that livers from Panx1-/- mice exhibited reduced ATP release, resulting in protected hepatocytes during preservation. The donor liver damage is decreased during SCS with blocking Panx1. Transmission electron microscopy revealed a decreased mitochondria-associated ER membranes (MAMs) and an improved mitochondria morphology. Mechanistically, Panx1 blockade upregulated the PI3K-AKT pathway and increased Bcl2 level to combat apoptosis during liver preservation. The data indicate that blocking Panx1 during preservation of the donor liver can effectively improve mitochondrial function, reducing cellular stress damage. Then cold ischemia and reperfusion-related injuries are obviously decreased in liver transplantation.

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来源期刊
CiteScore
18.70
自引率
4.50%
发文量
346
审稿时长
26 days
期刊介绍: The American Journal of Transplantation is a leading journal in the field of transplantation. It serves as a forum for debate and reassessment, an agent of change, and a major platform for promoting understanding, improving results, and advancing science. Published monthly, it provides an essential resource for researchers and clinicians worldwide. The journal publishes original articles, case reports, invited reviews, letters to the editor, critical reviews, news features, consensus documents, and guidelines over 12 issues a year. It covers all major subject areas in transplantation, including thoracic (heart, lung), abdominal (kidney, liver, pancreas, islets), tissue and stem cell transplantation, organ and tissue donation and preservation, tissue injury, repair, inflammation, and aging, histocompatibility, drugs and pharmacology, graft survival, and prevention of graft dysfunction and failure. It also explores ethical and social issues in the field.
期刊最新文献
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