Murakami Ken-ichi, Kaji Tatsuru, Shimono Ryuichi, Hayashida Yoshihiro, Matsufuji Hiroshi, Tsuyama Shinichiro, Maezono Rie, Kosai Ken-ichiro, Takamatsu Hideo
Department of Pediatric Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
Pediatr Surg Int. 2011 Aug;27(8):863-70. doi: 10.1007/s00383-011-2853-0. Epub 2011 Feb 3.
The aim of this study is to investigate the role of hepatic stellate cells (HSCs) and the effect of vitamin A administration on liver damage induced by bile duct ligation (BDL) and administration of CCl(4).
Two types of animal model were used; one was BDL as a model of biliary atresia, the other was CCl(4)-induced hepatic fibrosis. Pathological changes of the liver with or without administration of vitamin A were compared by light and electron microscopy with focusing on HSCs in each experimental group. Immunohistochemical examination was performed with anti-keratinocyte growth factor (KGF), anti-alpha-smooth muscle actin (α-SMA), and anti-glial fibrillary acidic protein (GFAP) antibodies, as markers of fibrosis.
On light microscopic findings, periportal inflammation with bile ductular proliferation was obvious in BDL group and pericentral necrosis with fatty degeneration was observed in CCl(4) group, both of which were ameliorated by subcutaneous injection of vitamin A. Electron microscopy showed lipid droplets were almost depleted in the HSCs treated with BDL or CCl(4), which improved with vitamin A administration. Immunohistochemistry demonstrated that enhanced expression of all three fibrotic markers in the BDL group was diminished by vitamin A administration.
Although most of our data are qualitative observation, vitamin A may ameliorate hepatic fibrosis in the BDL model by restoring vitamin A in the HSCs.
本研究旨在探讨肝星状细胞（HSCs）的作用以及给予维生素A对胆管结扎（BDL）和四氯化碳（CCl₄）诱导的肝损伤的影响。
使用两种动物模型；一种是作为胆道闭锁模型的BDL，另一种是CCl₄诱导的肝纤维化模型。通过光学显微镜和电子显微镜比较给予或未给予维生素A的肝脏的病理变化，重点关注每个实验组中的肝星状细胞。使用抗角质形成细胞生长因子（KGF）、抗α平滑肌肌动蛋白（α-SMA）和抗胶质纤维酸性蛋白（GFAP）抗体进行免疫组织化学检查，作为纤维化的标志物。
在光学显微镜下观察，BDL组可见门周炎症伴胆小管增生，CCl₄组可见中央周围坏死伴脂肪变性，皮下注射维生素A均可改善上述情况。电子显微镜显示，BDL或CCl₄处理的肝星状细胞中的脂滴几乎耗尽，给予维生素A后有所改善。免疫组织化学表明，维生素A给药可减少BDL组中所有三种纤维化标志物的表达增强。
尽管我们的大多数数据都是定性观察，但维生素A可能通过恢复肝星状细胞中的维生素A来改善BDL模型中的肝纤维化。
