口服二乙基亚硝胺诱导建立同系小鼠肝硬化模型

摘要

目的：尝试采用二乙基亚硝胺（DEN）喂饲小鼠成功诱导和建立小鼠肝硬化模型。方法选取纯系C57BL/6小鼠60只，随机分为实验组和对照组，各30只。实验组小鼠喂饲含DEN的饮水诱发肝硬化，对照组小鼠喂饲蒸馏水。采用HE染色、Masson染色等方法观察两组小鼠肝脏组织形态、纤维化，并连续30 d监测两组小鼠体质量变化，用行为学方法观察两组小鼠的自主运动差异判断其精神状态变化。结果随着喂饲DEN时间的增加，HE染色和Mas-son染色均显示实验组小鼠肝脏纤维化组织增生，肝硬化程度逐渐加重，各时间点的半定量评分系统评分与对照组比较，差异均有统计学意义（P<0.05）。实验组小鼠的体质量随着DEN喂饲时间的增加而明显降低，而对照组小鼠的体质量却略有增加，两组比较，差异有统计学意义（P<0.05）。实验组小鼠的运动总路程少于对照组，差异有统计学意义（P<0.05）。结论 DEN喂饲可诱发C57BL/6小鼠逐渐从肝纤维化到肝硬化，最终成功建立了前所未有的可作为研究人类肝硬化的一种理想动物模型。%Objective To attempt oral DEN to induce and establish hepatic cirrhosis model in C57BL/6 mice. Methods A total of 60 C57BL/6 mice were randomly divided into the experimental group and the control group ,30 of each group. The mice in the experimental group were fed with water contaning DEN while the control group with distilled water. The liver morpho-logical structure and fibrillation of the two groups were observed by HE and Masson dyeing. The body weight variation of mice in the two groups was measured in consecutive 30 days. The difference in autokinetic movement between the two groups was investi-gated by behavioral approach to judge their mental state changes. Results It showed with the longer DEN was given,the heavier the fibrosis tissue hyperplasia and hepatic cirrhosis degree displayed by HE and Masson dyeing. The semi-quantitative scoring system scoring at different time points in the experimental group had no statistical significance compared with that of the control group(P<0.05). The body weight declined obviously with increasing of feeding time in the experimental group while the mice in the control group slightly increased. There were statistical significance in difference (P<0.05). The behavioristics results showed that the total movement distance of the experimental mice was weaker than that of the normal mice ,whose difference had statistical significance(P<0.05). Conclusion DEN-induced hepatic cirrhosis model in C57BL/6 mice is successfully established from hep-atic fibrosis,and it can be used as an ideal animal model for the study of human hepatic cirrhosis.