Heavy Water (D2O) Containing Preservation Solution Reduces Hepatic Cold Preservation and Reperfusion Injury in an Isolated Perfused Rat Liver (IPRL) Model
Heavy Water (D2O) Containing Preservation Solution Reduces Hepatic Cold Preservation and Reperfusion Injury in an Isolated Perfused Rat Liver (IPRL) Model
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DOI：
10.3390/jcm8111818
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发表时间：
2019-11-01
影响因子：
3.9
通讯作者：
Taketomi, Akinobu
中科院分区：
文献类型：
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作者：
Shimada, Shingo;Fukai, Moto;Taketomi, Akinobu
背景：重水（D2 O）由于氘的同位素效应而具有多种生物学效应。我们先前报道了含D_2O溶液（Dsol）在大鼠心脏冷保存中的效果。在这里，我们评估Dsol是否减少肝脏冷保存和再灌注损伤。研究方法：将大鼠肝脏在威斯康星州大学（UW）溶液或Dsol中冷藏48小时，随后在分离的灌注大鼠肝脏上再灌注。评估移植物功能、损伤、灌注动力学、氧化应激和细胞骨架完整性。结果如下：在UW组中，严重的缺血和再灌注损伤（IRI）表现为组织病理学，较高的肝酶渗漏，门静脉阻力，和凋亡指数，耗氧量，较少的胆汁产生，能量电荷，和还原型谷胱甘肽（GSH）/氧化型谷胱甘肽（GSSG）的比例（与对照组相比）。Dsol组显示这些损伤显著改善（与UW组相比）。此外，细胞骨架紊乱的进展，在UW组中，所示的较少降解的α-胞衬蛋白和肌动蛋白解聚途径的失活，而这些变化在Dsol组中被显着抑制。结论：Dsol可降低肝脏长期冷保存再灌注后的IRI。这种保护主要是由于维持线粒体功能、细胞骨架完整性，导致限制氧化应激、凋亡和坏死途径。
Background: Heavy water (D2O) has many biological effects due to the isotope effect of deuterium. We previously reported the efficacy of D2O containing solution (Dsol) in the cold preservation of rat hearts. Here, we evaluated whether Dsol reduced hepatic cold preservation and reperfusion injury. Methods: Rat livers were subjected to 48-hour cold storage in University of Wisconsin (UW) solution or Dsol, and subsequently reperfused on an isolated perfused rat liver. Graft function, injury, perfusion kinetics, oxidative stress, and cytoskeletal integrity were assessed. Results: In the UW group, severe ischemia and reperfusion injury (IRI) was shown by histopathology, higher liver enzymes leakage, portal resistance, and apoptotic index, oxygen consumption, less bile production, energy charge, and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio (versus control). The Dsol group showed that these injuries were significantly ameliorated (versus the UW group). Furthermore, cytoskeletal derangement was progressed in the UW group, as shown by less degradation of alpha-Fodrin and by the inactivation of the actin depolymerization pathway, whereas these changes were significantly suppressed in the Dsol group. Conclusion: Dsol reduced hepatic IRI after extended cold preservation and subsequent reperfusion. The protection was primarily due to the maintenance of mitochondrial function, cytoskeletal integrity, leading to limiting oxidative stress, apoptosis, and necrosis pathways.