Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy
Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy
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DOI：
10.1007/s00418-012-0994-4
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发表时间：
2012-11-01
影响因子：
2.3
通讯作者：
Koji, Takehiko
中科院分区：
文献类型：
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作者：
An, Shucai;Soe, Kyaw;Koji, Takehiko
尽管铁过载与肝癌发生有关，但其确切机制尚不清楚。在本研究中，我们研究了用 3% 羰基铁的大鼠饲料喂养 3 个月的大鼠，在 70% 部分肝切除术 (PH) 后，铁过载对诱导肝细胞增殖的影响。在正常饮食的大鼠中，Ki-67标记指数（LI）在PH后24小时开始增加，掺入5-溴-2'-脱氧尿苷（BrdU）和磷酸组蛋白H3的增殖细胞核抗原（PCNA）的LI分别在PH后36和48小时达到最大值。在铁超载大鼠中，上述参数比正常饮食大鼠早12小时出现，从而缩短了G0-G1转变。有趣的是，在铁超载大鼠中，金属硫蛋白 (MT) 的核染色甚至在 0 小时就出现了，而金属硫蛋白 (MT) 对肝细胞增殖至关重要，而正常大鼠中 MT 表达发生在 6 小时。此外，在铁超载大鼠的 Kupffer 细胞中，0 小时时检测到核因子 kappa B (NF-kappa B) 表达，这是导致肝再生的重要早期事件。这些结果可能表明，超载的铁可能通过 MT 和 NF-κ B 的诱导，通过绕过参与肝脏再生启动的信号转导级联，使肝脏处于一种准备好再生的状态，以响应 PH。
Although iron overload is implicated in hepatocarcinogenesis, the precise mechanism was not known yet. In the present study, we investigated the effect of iron overload upon the induction of hepatocyte proliferation after 70 % partial hepatectomy (PH) in rats fed with rat chow with 3 % carbonyl iron for 3 months. In normal-diet rats, the increase in Ki-67 labeling index (LI) commenced at 24 h post-PH and the LIs of proliferating cell nuclear antigen (PCNA) incorporated 5-bromo-2'-deoxyuridine (BrdU) and phospho-histone H3 reached maximum values at 36 and 48 h after PH, respectively. In iron-overload rats, the above parameters occurred 12 h earlier compared to that of normal-diet rats, shortening the G0-G1 transition. Interestingly, nuclear staining for metallothionein (MT), which is essential for hepatocyte proliferation, was noted even at 0 h in iron-overload rats, while MT expression occurred at 6 h in the normal rats. Moreover, nuclear factor kappa B (NF-kappa B) expression, which is an essential early event leading to liver regeneration, was detected in Kupffer cells at 0 h in iron-overload rats. These results may indicate that overloaded iron, maybe through the induction of MT and NF-kappa B, may keep liver as a state ready to regenerate in response to PH, by bypassing signal transduction cascades involved in the initiation of liver regeneration.