Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea.
J Gastroenterol Hepatol. 2010 Nov;25(11):1769-76. doi: 10.1111/j.1440-1746.2010.06239.x.
The binucleation of hepatocytes, which was known as an important feature of liver growth and physiology, has been reported to be increased during the chronic oxidative injury stage and has been regarded as an age-related change of hepatic structures. Therefore, we investigated the binuclearity pattern in the livers of senescence marker proteins-30 (SMP30) knock-out (KO) mice compared with wild-type (WT) mice and vitamin C-treated KO (KO + VC) mice.
The WT, KO and KO + VC mice were fed a vitamin C free diet and VC(+) group mice were given vitamin C water containing 1.5 g/L of vitamin C, whereas VC(-) group was given normal drinking water without vitamin C, for 16 weeks.
In microscopic examination, the livers of KO mice showed a significantly increased number of binuclear hepatocytes compared with that of WT mice and KO + VC mice. KO mice also showed the most increased expression level of CYP2E1 and PCNA determined by immunohistochemistry and immunoblot analysis. Moreover, KO mice indicated the highest level of serum alanine aminotransferase and aspartate aminotransferase level in serum biochemical analysis. Accordingly, significantly decreased levels of reactive oxygen species, MDA (malondialdehyde) and HAE (4-hydroxyalkenals) were detected in KO + VC mice compared with KO mice.
Therefore, it is concluded that vitamin C deficiency induces an increase of CYP2E1 expression and elevated ROS production, which causes oxidative liver injury and the elevation of hepatocyte binucleation in SMP30 KO mice.
双核肝细胞曾被认为是肝脏生长和生理的重要特征，在慢性氧化损伤阶段其数量增加，并被认为是与年龄相关的肝结构变化。因此，我们研究了衰老标志物蛋白 30（SMP30）敲除（KO）小鼠与野生型（WT）小鼠和维生素 C 处理的 KO（KO+VC）小鼠肝脏的双核性模式。
WT、KO 和 KO+VC 组小鼠给予无维生素 C 饮食，VC（+）组小鼠给予含 1.5 g/L 维生素 C 的 VC 水，而 VC（-）组小鼠给予不含维生素 C 的正常饮用水，持续 16 周。
在显微镜检查中，与 WT 小鼠和 KO+VC 小鼠相比，KO 小鼠的双核肝细胞数量明显增加。免疫组织化学和免疫印迹分析显示，KO 小鼠还表现出 CYP2E1 和 PCNA 的表达水平显著增加。此外，KO 小鼠的血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平在血清生化分析中最高。相应地，与 KO 小鼠相比，KO+VC 小鼠中活性氧、MDA（丙二醛）和 HAE（4-羟烯醛）的水平显著降低。
因此，我们得出结论，维生素 C 缺乏会导致 CYP2E1 表达增加和 ROS 产生增加，从而导致 SMP30 KO 小鼠的氧化肝损伤和双核肝细胞数量增加。
