Ogata I, Fujiwara K
Life Sci. 1985 Dec 16;37(24):2269-73. doi: 10.1016/0024-3205(85)90017-7.
A single dose of dimethylnitrosamine dose-relatedly increased total hepatic hydroxyproline content in rats 14 days after the dosing. In cases of 35 mg/kg of dimethylnitrosamine, it increased rapidly to 1.7 times the normal level within 14 days. This increase persisted thereafter until 84 days. Hepatic collagen prolyl hydroxylase activity was 1.8 times the normal level by the fourth day after the dosing but normalized within 14 days. It decreased further to levels significantly lower than those in normal rats at 28, 56 and 84 days. Serum glutamic pyruvic transaminase activity was about 13 times the normal level at 2 days and normalized after 7 days. On histology, fiber developed in necrotic areas around the central veins after 7 days and remained after 28 days when the necrosis had already disappeared. These results suggest that abnormal collagen can continue to increase in the state of decreased collagen prolyl hydroxylase activity in the liver.
单次剂量的二甲基亚硝胺给药14天后，大鼠肝脏总羟脯氨酸含量呈剂量依赖性增加。给予35mg/kg二甲基亚硝胺时，14天内迅速增加至正常水平的1.7倍。此后这种增加一直持续到84天。给药后第4天，肝脏胶原脯氨酰羟化酶活性为正常水平的1.8倍，但在14天内恢复正常。在第28、56和84天时，其进一步降低至显著低于正常大鼠的水平。血清谷丙转氨酶活性在第2天时约为正常水平的13倍，7天后恢复正常。组织学检查显示，7天后中央静脉周围坏死区域出现纤维，28天时坏死已经消失，但纤维仍留存。这些结果表明，在肝脏胶原脯氨酰羟化酶活性降低的状态下，异常胶原仍可继续增加。
