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非心脏跳动供体猪肝移植中N-乙酰半胱氨酸的应用

N-acetylcysteine in pig liver transplantation from non-heart-beating donors.

作者信息

Manika A, Trinh T, Lagacé G, Dugas M A, Proulx F, Lepage G, Champagne J, Lavoie J C, Cousineau J, Russo P, Chartrand C, Yandza T

机构信息

Research Center, Sainte-Justine Hospital, Montreal, Quebec, Canada.

出版信息

Transplantation. 1999 Aug 15;68(3):327-30. doi: 10.1097/00007890-199908150-00002.

DOI:10.1097/00007890-199908150-00002
PMID:10459534
Abstract

Lipid peroxidation due to oxygen free radicals (OFR) seems to play a major role in loss of liver graft viability after warm ischemia, preservation, and transplantation. N-acetylcysteine (NAC) is an antioxidant that has a direct effect on OFR, and is also a glutathione precursor, another antioxidant. This study was designed to evaluate the efficacy of NAC in preventing ischemia-reperfusion damage of liver grafts harvested from non-heart-beating donors. Liver transplantation was performed on pigs divided into five groups: group 1 (control group; n=5) received livers from heart-beating donors; livers were subjected to 30 min of warm ischemia in groups 2 (n=3, no NAC) and group 3 (n=3; NAC treatment); warm ischemia time lasted 60 min in groups 4 (n=4; no NAC) and 5 (n=5; NAC treatment). Studied parameters included graft survival for more than 3 days, aspartate aminotransferase plasma levels, liver histology, and hepatic total glutathione concentrations. Graft survival was 100% in groups 1, 2, and 3, 0% in group 4, and 20% in group 5. NAC treatment did not influence initial mean aspartate aminotransferase release which was greater in warm ischemic livers than in controls. NAC treatment had no effect on liver hepatic total glutathione after reperfusion of animals receiving warm ischemic grants. Finally, no effect on liver histology was observed with NAC treatment. Our study suggests that in liver transplantation from non-heart-beating donors, NAC has no effect in both graft viability and lipid peroxidation. The role of OFR in primary dysfunction of transplanted warm ischemic livers remains controversial.

摘要

氧自由基(OFR)导致的脂质过氧化似乎在肝脏移植物在热缺血、保存及移植后丧失活力的过程中起主要作用。N-乙酰半胱氨酸(NAC)是一种抗氧化剂,对OFR有直接作用,同时也是另一种抗氧化剂谷胱甘肽的前体。本研究旨在评估NAC在预防从非心跳供体获取的肝脏移植物缺血再灌注损伤方面的疗效。将猪分为五组进行肝移植:第1组(对照组;n = 5)接受来自心跳供体的肝脏;第2组(n = 3,未用NAC)和第3组(n = 3;NAC处理)的肝脏经历30分钟热缺血;第4组(n = 4;未用NAC)和第5组(n = 5;NAC处理)的热缺血时间持续60分钟。研究参数包括移植物存活超过3天、血浆天冬氨酸转氨酶水平、肝脏组织学以及肝脏总谷胱甘肽浓度。第1、2和3组的移植物存活率为100%,第组4为0%,第5组为20%。NAC处理不影响最初的平均天冬氨酸转氨酶释放,热缺血肝脏中的该释放量高于对照组。NAC处理对接受热缺血移植物的动物再灌注后的肝脏总谷胱甘肽没有影响。最后,未观察到NAC处理对肝脏组织学有影响。我们的研究表明,在非心跳供体的肝移植中,NAC对移植物活力和脂质过氧化均无作用。OFR在移植的热缺血肝脏原发性功能障碍中的作用仍存在争议。

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N-acetylcysteine in pig liver transplantation from non-heart-beating donors.非心脏跳动供体猪肝移植中N-乙酰半胱氨酸的应用
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Experimental and clinical evidence for modification of hepatic ischaemia-reperfusion injury by N-acetylcysteine during major liver surgery.
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Liver Transpl. 2010 Nov;16(11):1267-77. doi: 10.1002/lt.22148.
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