Oe Hideaki, Kaido Toshimi, Mori Akira, Onodera Hisashi, Imamura Masayuki
Department of Surgery and Surgical Basic Science, Kyoto University School of Medicine, Kyoto Japan.
Hepatogastroenterology. 2005 Sep-Oct;52(65):1393-7.
BACKGROUND/AIMS: Hepatic oval cells play an important role in liver regeneration when proliferation of mature hepatocytes is inhibited. The aim of this study was to examine the effect of hepatocyte growth factor (HGF), or vascular endothelial growth factor (VEGF) on proliferation of oval cells in the Solt-Farber rat model.
One hour after 70% partial hepatectomy, 2-acetyl-aminofluorene-induced damaged rats were infected intravenously with recombinant adenoviral vectors, encoding rat HGF or human VEGF, or Escherichia coli beta-galactosidase as a control.
The plasma HGF concentrations in the HGF-transferred rats were elevated compared with the other groups at 4 and 7 days after hepatectomy. Oval cells were confirmed by positive staining of both cytokeratin-19 and alpha-fetoprotein. Oval cells around the portal tracts in the HGF or VEGF-transferred rats increased in number compared with the control rats at 7 and 9 days after hepatectomy. The proliferating cell nuclear antigen labeling indices of oval cells and the hepatic regeneration rate after hepatectomy were significantly augmented by the HGF or VEGF treatment. Moreover, cyclin E expression was elevated in the HGF-treated rats.
In the Solt-Farber rat model, HGF or VEGF gene injection effectively promoted liver regeneration after hepatectomy mainly with increased proliferation of hepatic oval cells.
背景/目的：当成熟肝细胞的增殖受到抑制时，肝卵圆细胞在肝脏再生中发挥重要作用。本研究的目的是检测肝细胞生长因子（HGF）或血管内皮生长因子（VEGF）对索尔特-法伯大鼠模型中卵圆细胞增殖的影响。
在70%部分肝切除术后1小时，用2-乙酰氨基芴诱导损伤的大鼠静脉注射编码大鼠HGF或人VEGF的重组腺病毒载体，或作为对照的大肠杆菌β-半乳糖苷酶。
肝切除术后4天和7天，HGF转导大鼠的血浆HGF浓度高于其他组。通过细胞角蛋白-19和甲胎蛋白的阳性染色证实了卵圆细胞。肝切除术后7天和9天，HGF或VEGF转导大鼠门管周围的卵圆细胞数量比对照大鼠增加。HGF或VEGF处理显著提高了卵圆细胞的增殖细胞核抗原标记指数和肝切除术后的肝脏再生率。此外，HGF处理的大鼠中细胞周期蛋白E表达升高。
在索尔特-法伯大鼠模型中，HGF或VEGF基因注射主要通过增加肝卵圆细胞的增殖有效促进了肝切除术后的肝脏再生。
