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氢气低温机器灌注减少大鼠肝脏局灶性损伤但不能恢复器官功能。

Hypothermic Machine Perfusion with Hydrogen Gas Reduces Focal Injury in Rat Livers but Fails to Restore Organ Function.

机构信息

Gastroenterological Surgery 1, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Department of Cell Physiology, Jikei University School of Medicine, Tokyo, Japan.

出版信息

Transplant Proc. 2023 May;55(4):1016-1020. doi: 10.1016/j.transproceed.2023.02.036. Epub 2023 Mar 21.

Abstract

BACKGROUND

We have previously reported the efficacy of post-reperfusion H gas treatment in cold storage (CS) and subsequent reperfusion of the rat liver. The present study aimed to evaluate the effect of H gas treatment during hypothermic machine perfusion (HMP) in rat livers retrieved from donation after circulatory death (DCD) and elucidate the mechanism of action of H gas.

METHODS

Liver grafts were procured from rats after 30 min of cardiopulmonary arrest. The graft was subjected to HMP for 3 hours at 7°C using Belzer MPS with or without dissolved H gas. The graft was reperfused using an isolated perfused rat liver apparatus at 37°C for 90 minutes. Perfusion kinetics, liver damage, function, apoptosis, and ultrastructure were evaluated.

RESULTS

Portal venous resistance, bile production, and oxygen consumption rates were identical in the CS, MP, and MP-H groups. Liver enzyme leakage was suppressed by MP (vs control), whereas H treatment did not show a combination effect. Histopathology revealed poorly stained areas with a structural deformity just below the liver surface in the CS and MP groups, whereas these findings disappeared in the MP-H group. The apoptotic index in the CS and MP groups was high but decreased in the MP-H group. Mitochondrial cristae were damaged in the CS group but preserved in the MP and MP-H groups.

CONCLUSIONS

In conclusion, HMP and H gas treatment are partly effective in DCD rat livers but insufficient. Hypothermic machine perfusion can improve focal microcirculation and preserve mitochondrial ultrastructure.

摘要

背景

我们之前报道了再灌注 H 气体处理在冷藏(CS)和随后的大鼠肝脏再灌注中的疗效。本研究旨在评估在低温机器灌注(HMP)期间 H 气体处理对来自心脏停搏后捐献(DCD)的大鼠肝脏的影响,并阐明 H 气体的作用机制。

方法

从心肺骤停 30 分钟后的大鼠中获取肝移植物。将移植物在 7°C 下用 Belzer MPS 进行 3 小时的 HMP,或用或不用溶解的 H 气体。在 37°C 下使用离体灌注大鼠肝脏装置对移植物进行 90 分钟的再灌注。评估灌注动力学、肝损伤、功能、凋亡和超微结构。

结果

门静脉阻力、胆汁生成和耗氧量在 CS、MP 和 MP-H 组中相同。MP(与对照相比)抑制了肝酶漏出,而 H 处理没有显示出组合效应。组织病理学显示 CS 和 MP 组中肝表面下方有染色不良的区域和结构变形,而 MP-H 组中这些发现消失了。CS 和 MP 组的凋亡指数较高,但在 MP-H 组中降低。CS 组的线粒体嵴受损,但在 MP 和 MP-H 组中得到了保留。

结论

总之,HMP 和 H 气体处理在 DCD 大鼠肝脏中部分有效但不足。低温机器灌注可以改善局灶性微循环并保存线粒体超微结构。

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