Etiology of Liver Steatosis Influences the Severity of Ischemia/Reperfusion Injury and Survival After Liver Transplantation in Rats
Etiology of Liver Steatosis Influences the Severity of Ischemia/Reperfusion Injury and Survival After Liver Transplantation in Rats
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DOI：
10.1002/lt.25814
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发表时间：
2020-08-25
影响因子：
4.6
通讯作者：
Uemoto, Shinji
中科院分区：
文献类型：
--
作者：
Miyachi, Yosuke;Yagi, Shintaro;Uemoto, Shinji
肝脂肪变性是肝移植中移植物处理的主要原因，尽管脂肪变性的程度通常是决定移植物可接受性的单一因素。我们研究了大鼠原位肝移植（奥尔特）中肝脏脂肪变性的原因如何影响移植物功能。采用2种脂肪变性肝移植物进行奥尔特：禁食和高营养（FHA）模型和蛋氨酸和胆碱缺乏饮食模型。FHA和4周喂养蛋氨酸和胆碱缺乏饮食（MCDD 4 wk）组显示出相似的肝脏甘油三酯水平，无脂肪性肝炎体征。因此，在以下实验中对两组进行比较。冷藏6 h后，FHA组的奥尔特7天存活率远低于MCDD 4 wk组（0%vs100%，P = 0.002）。冷藏1 h后，FHA组再灌注24 h时1区和2区的天冬氨酸转氨酶和丙氨酸转氨酶水平以及组织学损伤评分均高于正常肝组和MCDD 4 wk组。再灌注后FHA组肝内微循环和组织三磷酸腺苷水平显著降低。FHA组再灌注后肝细胞坏死，肝窦内皮细胞损伤，线粒体异常肿胀。MCDD 4 wk组再灌注前和再灌注后组织丙二醛水平均较高。然而，移植物上调几种抗氧化酶后不久再灌注。尽管脂肪变性程度相当，但两种脂肪变性模型具有相当独特的基础特征，对缺血/再灌注损伤和移植后存活表现出完全不同的反应。我们的研究结果表明，脂肪堆积的程度不是脂肪变性肝移植可用性的单一决定因素。
Liver steatosis is a leading cause of graft disposal in liver transplantation, though the degree of steatosis is often the single factor determining acceptability of the graft. We investigated how the cause of liver steatosis affects graft function in rat orthotopic liver transplantation (OLT). OLT was performed using 2 types of steatotic liver grafts: the fasting and hyperalimentation (FHA) model and the methionine- and choline-deficient diet models. The FHA and 4-week feeding of a methionine- and choline-deficient diet (MCDD4wk) groups showed similar liver triglyceride levels without signs of steatohepatitis. Therefore, the 2 groups were compared in the following experiment. With 6-hour cold storage, the 7-day survival rate after OLT was far worse in the FHA than in the MCDD4wk group (0% versus 100%,P = 0.002). With 1-hour cold storage, the FHA group showed higher aspartate aminotransferase and alanine aminotransferase levels and histological injury scores in zones 1 and 2 at 24 hours after reperfusion than the normal liver and MCDD4wk groups. Intrahepatic microcirculation and tissue adenosine triphosphate levels were significantly lower in the FHA group after reperfusion. Hepatocyte necrosis, sinusoidal endothelial cell injury, and abnormal swelling of the mitochondria were also found in the FHA group after reperfusion. Tissue malondialdehyde levels were higher in the MCDD4wk group before and after reperfusion. However, the grafts up-regulated several antioxidant enzymes soon after reperfusion. Even though the degree of steatosis was equivalent, the 2 liver steatosis models possessed quite unique basal characteristics and showed completely different responses against ischemia/reperfusion injury and survival after transplantation. Our results demonstrate that the degree of fat accumulation is not a single determinant for the usability of steatotic liver grafts.