Le Couteur D G, Rivory L P, Pond S M
University of Queensland, Department of Medicine, Princess Alexandra Hospital, Woolloongabba, Australia.
Transplantation. 1994 Sep 15;58(5):531-6. doi: 10.1097/00007890-199409150-00001.
During liver transplantation, donor livers are subject to hypoxia and reoxygenation. Recently, because of a shortage of suitable donors, the livers of older donors have been used for transplantation. In this study, we examined the influence of aging and nutritional state on hepatic intracellualr pH (pHi) and the susceptibility of the rat liver to hypoxia-reoxygenation injury. Perfused livers from fasted and fed, young (2-3 months) and aged (24-28 months) male Wistar rats were compared during 30 min of nitrogen hypoxia followed by 20 min of reoxygenation. Under control conditions, pHi was significantly lower and glucose release higher in livers from fed young rats (7.24 +/- 0.04, 3.4 +/- 1.8 mumol/min/g) than in those from fasted young (7.33 +/- 0.04, 0.0 +/- 1.3), fasted aged (7.32 +/- 0.03, -0.1 +/- 0.5), and fed aged rats (7.29 +/- 0.06, 0.9 +/- 1.0). In all groups, pHi fell by approximately 0.15 U during hypoxia. Lactate dehydrogenase (LDH) release from the livers of fed young livers was unaffected by hypoxia-reoxygenation as was that from the livers of fed aged rats, despite features that would be expected to predispose to injury (reduced glucose output and more alkaline pHi). In contrast, livers from fasted young and aged rats had substantially increased LDH release and reduced bile flow during hypoxia. There were no age-related differences in these parameters, but, during reoxygenation, LDH release was significantly less in the aged livers. These results indicate that the livers of fed rats are resistant to hypoxia-reoxygenation injury and that aging does not increase the susceptibility of the liver to injury in the fasted state.
在肝移植过程中，供体肝脏会经历缺氧和再灌注。近来，由于合适供体短缺，老年供体的肝脏也被用于移植。在本研究中，我们检测了衰老和营养状态对肝内细胞pH值（pHi）的影响以及大鼠肝脏对缺氧-再灌注损伤的易感性。对禁食和进食的年轻（2 - 3个月）和老年（24 - 28个月）雄性Wistar大鼠的灌注肝脏进行比较，先经历30分钟的氮气缺氧，随后再灌注20分钟。在对照条件下，进食的年轻大鼠肝脏的pHi显著低于禁食的年轻大鼠（7.24±0.04，3.4±1.8 μmol/min/g）、禁食的老年大鼠（7.32±0.03，-0.1±0.5）和进食的老年大鼠（7.29±0.06，0.9±1.0），而葡萄糖释放则更高。在所有组中，缺氧期间pHi下降约0.15单位。进食的年轻大鼠肝脏和进食的老年大鼠肝脏的乳酸脱氢酶（LDH）释放不受缺氧-再灌注的影响，尽管存在预期会导致损伤的特征（葡萄糖输出减少和pHi更偏碱性）。相比之下，禁食的年轻和老年大鼠肝脏在缺氧期间LDH释放大幅增加，胆汁流量减少。这些参数没有年龄相关差异，但在再灌注期间，老年肝脏的LDH释放显著减少。这些结果表明，进食大鼠的肝脏对缺氧-再灌注损伤具有抗性，并且衰老不会增加禁食状态下肝脏对损伤的易感性。
