中文摘要：

目的 探讨旨在降低死亡率的二甲基亚硝胺（DMN）肝纤维化改良造模方法及其病理特点.方法 大鼠分为常规方法造模组（常规组）与改良方法造模组（改良组）,每组再分为模型组与正常对照组,均设染毒后4周和8周共2个时间观察点.常规组造模以DMN 10μL/kg大鼠体重的剂量,腹腔注射,每周连续3d,连续4周,共12次;改良组同上剂量的DMN腹腔注射,每2d一次,连续4周,共14次.观察大鼠体重、肝体比与脾体比,试剂盒测定血清肝功能,HE染色与天狼猩红染色分别观察肝组织炎症与胶原沉积,盐酸水解法测定肝组织羟脯氨酸含量.结果 2种造模方法均在造模4周时形成典型的肝纤维化,模型大鼠的体重、肝体比、脾体比、血清肝功能等均有相应的变化趋势.与常规组比较,改良组模型大鼠造模8周后死亡率显著降低,肝细胞炎症坏死稍轻,而肝窦毛细血管化明显.结论 隔日1次腹腔注射较之连续3d腹腔注射DMN是一种较为稳定的肝纤维化改良造模方法,具有肝窦毛细血管化与小叶内纤维化的肝纤维化病理特征.

英文摘要：

Objective To explore an improved method of inducing rat liver fibrotic model by dimethylnitrosamine （DMN）, with a lower mortality than previous method, and to study the pathological characteristics of the modified liver fibrotic model. Methods The rats were divided into 2 groups： routine group and modified one, and each group was divided into normal control and model subgroups. All rats were observed at 4 w and 8 w after DMN intoxication. Rats in the routine group were injected intraperitoneally with DMN at a dose of 10 ,μL/kg for 3 consecutive days per week and lasting for 4 weeks, a total of 12 times DMN injections. Rats in the modified group were injected every other day with DMN in identical dose for 4 weeks, a total of 14 times DMN injections. The body weight, liver/body weight ratio, and spleen/body weight ratio of rats were observed and liver function were determined by commercial kits. Liver inflammation and collagen deposition were evaluated by histological examination with HE and Sirius red staining, respectively. The contents of hepatic hydroxypreline （Hyp） were measured by Jamall＇s method. Results Typical liver fibrosis was induced after 4 weeks of DMN exposure by both methods. There was a similar change tendency of the body weight, liver/body weight ratio, spleen/body weight ratio, and liver function in rats of both model subgroups. The mortality rate after 8 weeks in the modified group was significantly lower, the inflammation and necrosis of hepatocytes were slighter, and the hepatic sinusoid capillarization was more pronounced than that in routine group. Conclusion The modified method with intraperitoneal injection of DMN every other day is relatively stable than previous method with injection for 3 consecutive days per week. The hepatic fibrosis induced by the modified procedure is characterized by pronounced hepatic sinusoid eapillarization and hepatic lobular fibrosis.