Zimmermann H, Ganz P, Zimmermann A, Oguey D, Marti U, Reichen J
Department of Clinical Pharmacology, University of Berne, Switzerland.
J Hepatol. 1995 Oct;23(4):459-64. doi: 10.1016/0168-8278(95)80205-3.
Chronic bile duct obstruction in the rat leads to biliary cirrhosis but maintained hepatocellular mass. We have previously demonstrated translocation of epidermal growth factor receptor to nuclei. It remained unclear, however, whether this was due to hepatocyte proliferation and/or altered handling of epidermal growth factor receptor. Therefore, in the present investigation we stereologically estimated expression of proliferating cell nuclear antigen, a marker of the S phase of teh cell cycle at 1, 2, 3, 7, 14, 21 and 28 days after bile duct ligation. Proliferating cell nuclear antigen positive hepatocytes averaged 2.1 +/- 3.6% in sham-operated control animals. This increased to 20.7 +/- 6.4, 26.8 +/- 18.7, 31.3 +/- 23.9, 42.3 +/- 16.6 and 24.7 +/- 28.0% 3, 7, 14, 21 and 28 days after bile duct ligation, respectively (p<0.005 by ANOVA). This was correlated with the number of epidermal growth factor receptor positive nuclei (rs = 0.737) and inversely with the maximal binding capacity of epidermal growth factor to a crude plasma membrane fraction (rs = 0.697) reported previously. We conclude that bile duct ligation in the rat induces a significant hepatocellular proliferation as assessed by proliferating cell nuclear antigen expression and that this process could, at least in part, be related to increased nuclear expression of the epidermal growth factor receptor.
大鼠慢性胆管梗阻会导致胆汁性肝硬化，但肝细胞质量保持不变。我们之前已经证明表皮生长因子受体易位至细胞核。然而，尚不清楚这是由于肝细胞增殖和/或表皮生长因子受体处理方式改变所致。因此，在本研究中，我们采用体视学方法估计了胆管结扎后1、2、3、7、14、21和28天增殖细胞核抗原（一种细胞周期S期标志物）的表达。在假手术对照动物中，增殖细胞核抗原阳性肝细胞平均占2.1±3.6%。胆管结扎后3、7、14、21和28天，这一比例分别增至20.7±6.4%、26.8±18.7%、31.3±23.9%、42.3±16.6%和24.7±28.0%（方差分析，p<0.005）。这与表皮生长因子受体阳性细胞核数量相关（rs = 0.737），与先前报道的表皮生长因子与粗质膜组分的最大结合能力呈负相关（rs = 0.697）。我们得出结论，通过增殖细胞核抗原表达评估，大鼠胆管结扎可诱导显著的肝细胞增殖，且这一过程至少部分可能与表皮生长因子受体核表达增加有关。
