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首页> 外文期刊>American Journal of Physiology >Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype.
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Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype.

机译：对与冬眠表型有关的肝冷缺血-再灌注损伤的自然抵抗力。

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The success of liver grafts is currently limited by the length of time organs are cold preserved before transplant. Novel insights to improve viability of cold-stored organs may emerge from studies with animals that naturally experience low body temperatures (T(b)) for extended periods. In this study, we tested whether livers from hibernating ground squirrels tolerate cold ischemia-warm reperfusion (cold I/R) for longer times and with better quality than livers from rats or summer squirrels. Hibernators were used when torpid (T(b) < 10 degrees C) or aroused (T(b) = 37 degrees C). Livers were stored at 4 degrees C in University of Wisconsin solution for 0-72 h and then reperfused with 37 degrees C buffer in vitro. Lactate dehydrogenase (LDH) release after 60 min was increased 37-fold in rat livers after 72 h cold I/R but only 10-fold in summer livers and approximately three- to sixfold in torpid and aroused hibernator livers, despite twofold higher total LDH content in livers from hibernators compared with rats or summer squirrels. Reperfusion for up to 240 min had the least effect on LDH release in livers from hibernators and the greatest effect in rats. Compared with rats or summer squirrels, livers from hibernators after 72 h cold I/R showed better maintenance of mitochondrial respiration, bile production, and sinusoidal lining cell viability, as well as lower vascular resistance and Kupffer cell phagocytosis. These results demonstrate that the hibernation phenotype in ground squirrels confers superior resistance to liver cold I/R injury compared with rats and summer squirrels. Because hibernation-induced protection is not dependent on animals being in the torpid state, the mechanisms responsible for this effect may provide new strategies for liver preservation in humans.
机译：目前，肝移植的成功受到器官在移植前冷藏的时间长度的限制。对动物进行长时间自然低温观察的研究可能会产生提高冷藏器官生存能力的新颖见解。在这项研究中，我们测试了冬眠松鼠的肝脏是否比大鼠或夏季松鼠的肝脏耐受更长的时间，并且具有更好的质量，可以耐受冷缺血-热再灌注。冬眠（T（b）<10摄氏度）或激起（T（b）= 37摄氏度）时使用冬眠器。将肝在威斯康星大学溶液中于4℃下保存0-72h，然后在体外用37℃缓冲液再灌注。低温I / R后60分钟后，大鼠肝脏中的乳酸脱氢酶（LDH）释放增加了37倍，而夏季肝脏中乳酸的脱氢酶（LDH）增加了两倍，而夏季肝脏仅增加了10倍，而冬眠和唤醒的冬眠者肝脏中释放了约3至6倍与大鼠或夏季松鼠相比，冬眠者肝脏中的胆固醇含量更高。再灌注长达240分钟，对冬眠动物肝脏中LDH释放的影响最小，而对大鼠的影响最大。与大鼠或夏季的松鼠相比，冷I / R后的冬眠者肝脏表现出更好的线粒体呼吸维持，胆汁生成和正弦衬里细胞活力，以及更低的血管阻力和库普弗细胞吞噬作用。这些结果表明，与大鼠和夏季松鼠相比，地松鼠的冬眠表型对肝脏感冒I / R损伤具有更好的抵抗力。由于冬眠诱导的保护并不依赖于处于龟to状态的动物，因此造成这种效应的机制可能为人类肝脏保存提供新的策略。

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