Gong Jin, Lao Xue-Jun, Zhang Shui-Jun, Chen Shi
Department of Surgery, First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
Hepatobiliary Pancreat Dis Int. 2008 Oct;7(5):481-4.
Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs.
One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8), controls 1, 2 and 3 (C1, C2, C3, n=16), and experimental 1, 2 and 3 (E(1), E(2), E(3), n=16). For groups C(1) and E(1), C(2) and E(2), and C(3) and E(3), the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 degree centigrade Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation.
At 1 hour after portal vein reperfusion, the levels of NO in groups E(1), E(2), E(3) and C(1), C(2), C(3) were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P<0.05). At 1, 3, and 24 hours, the levels of NO in groups E(1), E(2), E(3) were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C(1), C(2), C(3) (P<0.05). The levels of NO in groups C(2) and C(3) were lower than in group C1 (P<0.05), and the level of NO in group C(3) was lower than in group C(2) (P<0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E1, E2, E3 were lower than those in the corresponding control groups (C(1), C(2), C(3)) (P<0.05). The levels of plasma ET, serum ALT, and AST were lower in group C(3) than in groups C(1) and C(2) (P<0.05). Pathological changes in groups E(1), E(2), E(3) were milder than those in the corresponding experimental control groups (C(1), C(2), C(3)).
The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.
尽管使用非心脏跳动供体（NHBDs）可以缩小器官供需之间不断扩大的差距，但其在肝移植中的应用因原发性移植物丢失的高发生率而受到限制。预防NHBDs中的肝损伤将有利于移植结果。本研究旨在评估L-精氨酸对NHBDs肝移植物的保护作用。
104只Wistar大鼠随机分为7组：正常对照组（n = 8），对照组1、2和3（C1、C2、C3，n = 16），以及实验组1、2和3（E1、E2、E3，n = 16）。对于C1和E1组、C2和E2组以及C3和E3组，热缺血时间分别为0、30和45分钟。在每个实验组中，肝移植物用含1 mmol/L L-精氨酸的4摄氏度Euro - collins溶液冲洗并保存1小时。每个实验组的受体在门静脉再灌注前10分钟经尾静脉注射L-精氨酸（10 mg/kg体重）。每个实验对照组的供体和受体用生理盐水处理。然后进行移植。在门静脉再灌注后1、3和24小时，采集血样以测定丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、一氧化氮（NO）和血浆内皮素（ET）水平。在门静脉再灌注后3小时，将移植物样本固定在2.5%戊二醛中用于电子显微镜观察。
门静脉再灌注后1小时，E1、E2、E3组和C1、C2、C3组的NO水平较低，而血浆ET、血清ALT和AST水平高于正常对照组（P < 0.05）。在1、3和24小时，E1、E2、E3组的NO水平较高，而血浆ET、血清ALT和AST水平低于相应对照组（C1、C2、C3）（P < 0.05）。C2和C3组的NO水平低于C1组（P < 0.05），C3组的NO水平低于C2组（P < 0.05）。在1、3和24小时，E1、E2、E3组的血浆ET、血清ALT和AST水平低于相应对照组（C1、C2、C3）（P < 0.05）。C3组的血浆ET、血清ALT和AST水平低于C1和C2组（P < 0.05）。E1、E2、E3组的病理变化比相应实验对照组（C1、C2、C3）更轻。
NO与ET之间的失衡在NHBDs肝移植物缺血再灌注损伤的发生中起重要作用。L-精氨酸可通过改善NO与ET之间的平衡减轻NHBDs肝移植物的损伤。
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