Hou Zhengsheng, Yanaga Katsuhiko, Kamohara Yukio, Eguchi Susumu, Tsutsumi Ryuji, Furui Junichiro, Kanematsu Takashi
Department of Transplantation and Digestive Surgery, Graduate School of Biomedical Science, Nagasaki University, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan
Hepatol Res. 2003 May;26(1):40-46. doi: 10.1016/s1386-6346(02)00334-0.
In the present study, the effect of FR167653, a novel suppressive agent against interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), on liver regeneration was investigated in rats after partial hepatectomy (PH). Doses of 1, 3 and 5 mg/kg per h FR167653 (FR-1, FR-3 and FR-5, respectively) were given intravenously 30 min before PH, while the control was given normal saline. Serum chemistries were serially monitored, and liver regeneration was evaluated by remnant liver weight ratio, proliferating cell nuclear antigen (PCNA) labeling index and mitotic index. Accumulation of IL-1beta and TNF-alpha messenger RNA (mRNA) in the remnant liver was also measured. In FR167653-treated groups, the releases of alanine transaminase (ALT) and aspartate transaminase (AST) were lower. The PCNA labeling index was enhanced by FR167653-administration in a dose-dependent manner, FR-3 and FR-5 groups showed significantly higher peak DNA synthesis than the control group at 24 h post-PH (P<0.01). The mitotic index was also enhanced by FR167653-administration in a dose-dependent manner. In FR-5 group, the remnant liver weight ratio was significantly higher than that in the control group (P<0.05). The accumulation of IL-1beta messenger RNA (mRNA) in the remnant liver was obviously suppressed in FR-3 and FR-5 groups, but the expression of TNF-alpha mRNA was not apparently reduced. In conclusion, FR167653 ameliorates liver injury and enhances liver regeneration after PH in rats.
在本研究中，我们探讨了新型白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）抑制剂FR167653对大鼠部分肝切除（PH）后肝再生的影响。在PH前30分钟静脉注射每小时1、3和5毫克/千克剂量的FR167653（分别为FR-1、FR-3和FR-5），对照组注射生理盐水。连续监测血清生化指标，并通过残余肝重量比、增殖细胞核抗原（PCNA）标记指数和有丝分裂指数评估肝再生情况。还测量了残余肝中IL-1β和TNF-α信使核糖核酸（mRNA）的积累。在FR167653治疗组中，丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）的释放较低。给予FR167653后，PCNA标记指数呈剂量依赖性增强，FR-3和FR-5组在PH后24小时的DNA合成峰值显著高于对照组（P<0.01）。给予FR167653后，有丝分裂指数也呈剂量依赖性增强。在FR-5组中，残余肝重量比显著高于对照组（P<0.05）。FR-3和FR-5组残余肝中IL-1β信使核糖核酸（mRNA）的积累明显受到抑制，但TNF-α mRNA的表达没有明显降低。总之，FR167653可改善大鼠PH后的肝损伤并增强肝再生。
