腹腔注射四氯化碳致Wistar大鼠肝纤维化模型制作的探讨

Approach of Hepatic Fibrosis Model of Wistar Rats Induced by Carbon Tetrachloride with Intraperitoneal Injection

目的:通过筛选腹腔注射CCl_4致Wistar大鼠肝纤维化模型的最佳剂量,追踪观察模型大鼠血清及肝组织学指标的时效及量效关系。方法:采用随机对照分组的方法,对各模型组的Wistar大鼠给予不同剂量的CCl_4,进行腹腔注射,每周2次,共8周。分别于第3、6、8周随机处死动物总数的三分之一,检测血清ALT、AST水平及肝组织SOD活性、MDA含量的变化。另取肝组织进行病理切片镜下观察,以明确其肝纤维化程度。结果:造模8周间,与A组比较,各模型剂量组血清ALT、AST水平均显著升高(P<0.01),肝组织SOD活性显著降低(P<0.01),MDA含量显著升高(P<0.01)。造模结束,D组共死亡6只,肝腹水2只;C组死亡2只;B组死亡1只。随着CCl_4剂量的增加,大鼠肝组织的病理损伤明显加重。结论:该方法肝损伤明显、死亡率低、周期短、对其他重要脏器影响小,可作为慢性肝损伤、肝纤维化较好的模型。

Objective： To optimize the carbon tetrachloride-induced hepatic fibrosis in the rats with respect to dose and time course. Method： Carbon tetrachloride with different dosage was given to wistar rats by aintraperitoneal injection for eight weeks, twice per week. ALT, AST in the serum and the activity of SOD, MDA in the liver were analyzed in the third, sixth and eighth week respectively. Moreover,rats liver were observed with routine pathology technique ,the rats livers＇morphological changes were determined after administration. Result： Compared with the control group, the level of serum ALT and AST in model group were increased significantly （P 〈0.01 ） ;the activity of SOD decreased significantly （P 〈0. 01 ） and the content of MDA increased significantly （P 〈0. 01 ）. Conclusion： A meliorated hepatic fibrosis model of rat was established,which has definite liver injury with lower mortality rate, short time and less damnification to other organs, and can be used for the mechanism and treatment research of hepatic fibrosis.