CCl_4和PS两种SD大鼠模型肝纤维化进程时效关系对比研究

Time-Effect Study of Two Animal Models of Rats with Hepatic Fibrosis

目的 比较CCl4 法和PS法两种肝纤维化制模方法在肝纤维化形成进程中时效关系和病理学特征。方法 采用CCl4 和PS法制作SD大鼠肝纤维化模型 ,分别观察在造模第 6、10、14、2 0周时肝脏组病学特征 ,Masson三色染色和计算机图像分析系统进行分析。结果 CCl4 法于制模第 6周即可见肝脏假小叶形成 ,于第 10周始最为典型 ;随着假小叶的形成和造模方法停止 ,肝脏病理结构变化趋于稳定 ;肝细胞脂肪变性尤为突出 ,与模型制作进程相平行。PS法于造模第 10周即造模结束时方见纤维间隔形成 ,造模虽已停止但肝纤维化进程加速完成 ,肝组织分隔严重 ,假小叶形成较多并进展到第 2 0周 ;制模自始至终 ,肝细胞未见明显脂肪变性。结论 CCl4 和PS两种制模方法在肝纤维化形成进程中所表现出的时效关系和病理特征有所不同 ,提示两种制模方法在形成肝纤维化机制方面有所不同。结合使用两种方法研究肝纤维化更为合理 ;以抗肝纤维化干预因子进行干预研究时 ,干预因子的持续时间宜延长至肝纤维化形成之高峰期或之后 ,持续时间至少 14周 ;预防和治疗用药干预研究时 ,其起始时间宜分别以造模开始前 4周和造模停止前

Objective To analyze the differences between the two kinds of hepatic fibrotic animal models in time effect and pathologic features in the course of development of liver fibrosis. Methods\ CCl 4 and PS ten week methods were used to make rat models of liver fibrosis. The development of pathologic features of liver fibrosis was observed at 6, 10, 14 and 20 weeks of model making respectively, and these presentations were analyzed by Masson stain and computerized image analyzing system. Results\ In CCl 4 method group, fibrotic pseudolobuli developed at 6 weeks during model making, became typical at 10 weeks, and got tranquilization thereafter, with ballooning degeneration of liver cells outstanding. On the contrary in PS method group, fibrosis occurred late in 10 weeks during model making, and developed from 10 weeks through 14 weeks though the model making had stopped; meanwhile ballooning degeneration was not presented. Conclusion\ There was indeed something different in the development of liver fibrosis in time effect relation and pathologic features between the two groups of model making. This indicated different mechanisms in the pathogenesis of liver fibrosis. The two methods of model making should be combined in the coming animal study of liver fibrosis; the prophylactic and treatment studies by anti fibrotic drugs should last no less than 14 weeks, and should begin 4 weeks ahead of the beginning of and the end of model making.