Cyclin expression in the atrophying and proliferating lobes of the liver after portal vein branch ligation and hepatectomy in rats.
Cyclin expression in the atrophying and proliferating lobes of the liver after portal vein branch ligation and hepatectomy in rats.
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DOI：
10.1016/j.jss.2003.11.020
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发表时间：
2004-07
期刊：
影响因子：
--
通讯作者：
J. Ueda;K. Chijiiwa;K. Nakano
中科院分区：
文献类型：
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作者：
J. Ueda;K. Chijiiwa;K. Nakano
背景门静脉分支结扎导致门静脉结扎肝叶（PVL）萎缩和肝脏非结扎叶（PVNL）增殖。然而，门静脉分支结扎后PVL萎缩和PVNL增殖的机制尚未阐明，除了白细胞介素6（IL-6）、核因子κB（NF-κB）、信号转导和转录激活子3（STAT3）以及立即早期基因表达在PVL和PVNL中类似地被诱导之外。因此，目前尚不清楚是什么因素导致随后的萎缩和增殖。材料与方法雄性Wistar大鼠随机分为门静脉分支结扎组和部分肝切除组。门静脉分支结扎组，结扎供应肝正中叶和左外叶的门静脉分支。在部分肝切除组中，切除相应的肝叶。我们检查了门静脉分支结扎后PVL和PVNL中细胞周期蛋白的表达，并与部分肝切除后剩余肝脏（HEP）中细胞周期蛋白的表达进行比较。分别采用RT-PCR和Western blotting分析Cyclin D1、E、A mRNA和蛋白表达。结果PVL中Cyclin D1和A mRNA和蛋白表达不上调，而PVNL和HEP中Cyclin D1和A mRNA和蛋白表达上调。 18 h 时 PVL 中 Cyclin D1 mRNA 和蛋白表达显着低于 PVNL 和 HEP。 36 h时PVL中cyclin A的mRNA和蛋白表达水平显着低于PVNL和HEP。与 HEP 相比，PVNL 中的肝脏再生（通过相对肝脏重量、胸苷掺入 DNA 和增殖细胞核抗原 (PCNA) 标记指数进行评估）显着延迟。 12小时和18小时时，PVNL中的细胞周期蛋白D1 mRNA和蛋白表达分别显着低于HEP。结论细胞周期进展可能在G1期受到抑制，同时PVL中的细胞周期蛋白D1表达受损，从而导致萎缩。与 HEP 相比，PVNL 的肝脏增殖延迟这一事实可能是由于细胞周期蛋白 D1 的延迟表达所致。
BACKGROUNDPortal vein branch ligation causes atrophy of the portal vein ligated lobes (PVL) and proliferation of the nonligated lobes (PVNL) of the liver. However, the mechanisms underlying atrophy of the PVL and proliferation of PVNL after portal vein branch ligation have not been clarified except that interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and immediate-early gene expression are similarly induced in both the PVL and the PVNL. Thus, it is still unclear what factors cause the subsequent atrophy and proliferation.MATERIALS AND METHODSMale Wistar rats were randomly separated into a portal vein branch ligation group and partial hepatectomy group. In the portal vein branch ligation group, the branch of portal vein supplying the median and left lateral lobes of the liver was ligated. In the partial hepatectomy group, the correspondent lobes of the liver were excised. We examined cyclin expression in the PVL and PVNL after portal vein branch ligation in comparison to cyclin expression in the remaining liver (HEP) after partial hepatectomy. Cyclin D1, E, and A mRNA and protein expressions were analyzed by RT-PCR and Western blotting, respectively.RESULTSThe mRNA and protein expressions of cyclin D1 and A were not up-regulated in the PVL, whereas those in the PVNL and HEP were up-regulated. Cyclin D1 mRNA and protein expressions were significantly lower in the PVL than in the PVNL and HEP at 18 h. The levels of mRNA and protein expression of cyclin A were significantly lower in the PVL than in the PVNL and HEP at 36 h. Liver regeneration, assessed by the relative liver weight, thymidine incorporation into DNA, and proliferating cell nuclear antigen (PCNA) labeling index was delayed significantly in the PVNL compared to that in the HEP. Cyclin D1 mRNA and protein expressions were significantly lower in the PVNL than in the HEP at 12 and 18 h, respectively.CONCLUSIONSCell-cycle progression might be inhibited at G1-phase accompanied by impaired cyclin D1 expression in the PVL, which results in atrophy. The fact that liver proliferation of the PVNL is delayed in comparison to that of the HEP is likely due to delayed expression of cyclin D1.