Kobayashi J, Takeyoshi I, Ohwada S, Iwanami K, Matsumoto K, Muramoto M, Morishita Y
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Hepatology. 1998 Aug;28(2):459-65. doi: 10.1002/hep.510280225.
Interleukin-1 (IL-1) and tumor necrosis factor (TNF) are cytokines commonly associated with inflammatory conditions such as hepatic injury after ischemia-reperfusion. FR167653 has been characterized as a potent suppressant of IL-1beta and TNF-alpha production. In this study, we evaluated the effect of FR167653 in an extended liver resection with ischemia in a dog model. The right portal pedicle was clamped for 60 minutes, while the left portal branch was patent to avoid portal congestion. Following reperfusion, 75% of the liver (including the right central, quadrate, left central, left lateral, and papillary lobes) were resected. Animals were divided into two groups: a control group (n = 10), and a FR-treated group (n = 6) in which FR167653 was administered via the portal vein. Hepatic venous blood was collected to measure alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), purine nucleoside phosphorylase (PNP), and hyaluronic acid (HA) levels, and IL-1beta expression was also measured by reverse-transcriptase polymerase chain reaction (RT-PCR). ALT, AST, LDH, PNP, and HA levels after reperfusion were significantly lower (P < .05) in the FR-treated group than in the control group, and the FR-treated group showed inhibited IL-1beta expression. Liver tissue blood flow, measured by a laser Doppler flow meter, was kept higher in the FR-treated group than in the control group. Histologically, tissue damage was mild in the FR-treated group. The 2-day survival rate was statistically better (P < .05) in the FR-treated group than in the control group. We conclude that FR167653 provides a protective effect for liver parenchyma and sinusoidal endothelial cells in extended liver resection with ischemia.
白细胞介素-1（IL-1）和肿瘤坏死因子（TNF）是通常与诸如缺血再灌注后肝损伤等炎症状态相关的细胞因子。FR167653已被表征为IL-1β和TNF-α产生的强效抑制剂。在本研究中，我们在犬模型的延长肝切除并伴有缺血的情况下评估了FR167653的作用。右门静脉蒂夹闭60分钟，而左门静脉分支保持通畅以避免门静脉淤血。再灌注后，切除75%的肝脏（包括右中叶、方叶、左中叶、左外叶和乳头叶）。动物分为两组：对照组（n = 10）和FR治疗组（n = 6），FR治疗组经门静脉给予FR167653。收集肝静脉血以测量丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）、嘌呤核苷磷酸化酶（PNP）和透明质酸（HA）水平，并且还通过逆转录聚合酶链反应（RT-PCR）测量IL-1β表达。再灌注后，FR治疗组的ALT、AST、LDH、PNP和HA水平显著低于对照组（P < 0.05），并且FR治疗组显示出IL-1β表达受到抑制。通过激光多普勒血流仪测量的肝组织血流量，FR治疗组高于对照组。组织学上，FR治疗组的组织损伤较轻。FR治疗组的2天生存率在统计学上优于对照组（P < 0.05）。我们得出结论，FR167653在伴有缺血的延长肝切除中为肝实质和肝窦内皮细胞提供保护作用。
