Iwazaki S, Takeyoshi I, Ohwada S, Sunose Y, Tsutsumi H, Kawashima Y, Matsumoto K, Morishita Y
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Gunma, Japan.
Hepatogastroenterology. 2001 Jan-Feb;48(37):197-202.
BACKGROUND/AIMS: Platelet-activating factor is one of the most potent phospholipid mediators associated with inflammatory conditions such as ischemia and reperfusion injury. FR128998 (FR) is a novel platelet-activating factor receptor antagonist. In this study, we evaluated the effect of FR during an extended liver resection with ischemia in a canine model.
Animals were divided into two groups: the control group (n = 8), and the FR-treated group (n = 7) in which FR was administered via the portal vein. While the right portal pedicle was clamped for 60 min, the left portal branch remained patent to avoid splanchnic congestion. Following reperfusion, 75% of the liver (including the right central, quadrate, left central, left lateral, and papillary lobes) was resected. Hepatic venous blood was collected to measure GPT, GOT, and LDH levels. Hepatic tissue blood flow was measured by a laser Doppler flow meter. The liver specimen was harvested for histological study.
GPT, GOT, and LDH levels after reperfusion were significantly (P < 0.05) lower in the FR-treated group than in the control group. Hepatic tissue blood flow was maintained significantly (P < 0.05) higher in the FR-treated group than in the control group. Histologically, accumulation of polymorphonuclear neutrophils significantly (P < 0.05) decreased in the FR-treated group compared with the control group. The 2-day survival rate was statistically (P < 0.05) better in the FR-treated group than in the control group.
FR128998 provides a protective effect for liver parenchyma and sinusoidal endothelial cells during extended liver resection with ischemia.
背景/目的：血小板活化因子是与诸如缺血和再灌注损伤等炎症状态相关的最有效的磷脂介质之一。FR128998（FR）是一种新型血小板活化因子受体拮抗剂。在本研究中，我们在犬模型的长时间肝脏缺血切除术中评估了FR的作用。
动物分为两组：对照组（n = 8）和经门静脉给予FR的FR治疗组（n = 7）。在右门静脉蒂夹闭60分钟时，左门静脉分支保持通畅以避免内脏充血。再灌注后，切除75%的肝脏（包括右中央叶、方叶、左中央叶、左外侧叶和乳头叶）。收集肝静脉血以测量GPT、GOT和LDH水平。用激光多普勒流量计测量肝组织血流量。采集肝脏标本进行组织学研究。
再灌注后，FR治疗组的GPT、GOT和LDH水平显著低于对照组（P < 0.05）。FR治疗组的肝组织血流量显著高于对照组（P < 0.05）。组织学上，与对照组相比，FR治疗组多形核中性粒细胞的积聚显著减少（P < 应为0.05）。FR治疗组的2天生存率在统计学上显著高于对照组（P < 0.05）。
在长时间肝脏缺血切除术中，FR128998对肝实质和肝血窦内皮细胞具有保护作用。 （注：此处原文有误，P < 0.05 重复出现，推测应为不同数值或其他表述，翻译时保留原文错误）
