1(st) Department of Surgery, Semmelweis University, Budapest, Hungary.
J Surg Res. 2011 Mar;166(1):95-103. doi: 10.1016/j.jss.2009.09.047. Epub 2009 Oct 22.
Surgical methods that reduce bleeding during major hepatic resections lead to warm ischemia-reperfusion (I-R) injury of the liver. This is well known to have a considerable impact on the postoperative outcome. Much research work has been done to develop possible protective techniques. We aimed to investigate the effectivity of L-alanyl-L-glutamine dipeptide pretreatment in an animal model of hepatic I-R injury.
Male Wistar rats underwent normothermic, 60 min segmental liver ischemia followed by 24 h of reperfusion. The animals (n=30) were divided into three experimental groups: sham operated, I-R, and glutamine (Gln) pretreated. Twenty-four h prior to I-R injury, rats in the Gln group received 500 mg/kg Dipeptiven infusion as glutamine pretreatment. Hepatic microcirculation during the first hour of reperfusion was monitored by noninvasive laser Doppler flowmeter. After a 24-h reperfusion period, liver tissue was analyzed by histologic and immunohistochemical assessments. Serum necroenzyme and antioxidant levels were measured.
In the Gln group, the integral of the reperfusion curve (RA) and the plateau maximum (PM(10)) of the flow graph showed improving tendency (RA: P=0.096; PM(10): P=0.084). Severity of histologic damage was reduced. Serum necroenzymes (ALT: P=0.042, AST: P=0.044) were significantly lower. Chemiluminescent intensity of liver and plasma was significantly decreased (P=0.0003 and P=0.0496). Further spectrophotometric analysis of liver homogenate samples also showed significant improvement of the redox homeostasis.
Our results suggest that L-alanyl-L-glutamine dipeptide pretreatment given 24 h prior to I-R injury could be an effective method to reduce liver damage caused by hepatic inflow occlusion.
减少肝大部切除术出血的手术方法会导致肝脏热缺血再灌注（I-R）损伤。这对术后结果有很大影响，已经做了很多研究工作来开发可能的保护技术。我们旨在研究 L-丙氨酰-L-谷氨酰胺二肽预处理对肝 I-R 损伤动物模型的效果。
雄性 Wistar 大鼠进行常温、60 分钟节段性肝缺血，再灌注 24 小时。将动物（n=30）分为三组：假手术组、I-R 组和谷氨酰胺（Gln）预处理组。在 I-R 损伤前 24 小时，Gln 组大鼠接受 500mg/kg Dipeptiven 输注作为谷氨酰胺预处理。在再灌注的头 1 小时内通过非侵入性激光多普勒血流仪监测肝微循环。再灌注 24 小时后，通过组织学和免疫组织化学评估分析肝组织。测量血清坏死酶和抗氧化水平。
在 Gln 组，再灌注曲线（RA）的积分和流量图的平台最大值（PM(10)）显示出改善趋势（RA：P=0.096；PM(10)：P=0.084）。组织学损伤严重程度降低。血清坏死酶（ALT：P=0.042，AST：P=0.044）显著降低。肝和血浆的化学发光强度显著降低（P=0.0003 和 P=0.0496）。进一步对肝匀浆样本的分光光度分析也表明氧化还原稳态显著改善。
我们的结果表明，I-R 损伤前 24 小时给予 L-丙氨酰-L-谷氨酰胺二肽预处理可能是减少肝血流阻断引起的肝损伤的有效方法。
