A new suppressive agent against interleukin-1β and tumor necrosis factor-α enhances liver regeneration after partial hepatectomy in rats
A new suppressive agent against interleukin-1β and tumor necrosis factor-α enhances liver regeneration after partial hepatectomy in rats
复制标题
DOI：
10.1016/s1386-6346(02)00334-0
复制
发表时间：
2003-05-01
影响因子：
4.2
通讯作者：
Kanematsu, T
中科院分区：
文献类型：
--
作者：
Hou, ZS;Yanaga, K;Kanematsu, T
在本研究中，研究了 FR 167653（一种新型白介素 1 β (IL-1 β) 和肿瘤坏死因子 α (TNF-α) 抑制剂）对部分肝切除 (PH) 后大鼠肝再生的影响。在PH前30分钟静脉内给予剂量为1、3和5mg/kg/h的FR167653（分别为FR-1、FR-3和FR-5），而对照给予生理盐水。连续监测血清化学成分，并通过残肝重量比、增殖细胞核抗原（PCNA）标记指数和有丝分裂指数评估肝再生。还测量了残余肝脏中 IL-1β 和 TNF-α 信使 RNA (mRNA) 的积累。在 FR 167653 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。 FR167653给药以剂量依赖性方式增强PCNA标记指数，FR-3和FR-5组在PH后24小时表现出显着高于对照组的峰值DNA合成（P < 0.01）。有丝分裂指数也通过FR167653施用以剂量依赖性方式增强。 FR-5组残肝重量比显着高于对照组（P < 0.05）。 FR-3和FR-5组残肝中IL-1β信使RNA（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。 (C) 2003 Elsevier Science B.V. 保留所有权利。
In the present study, the effect of FR 167653, 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 FR 167653-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. (C) 2003 Elsevier Science B.V. All rights reserved.