四氯化碳不同给药途径复合乙醇诱导大鼠肝纤维化模型的研究

Preparation of hepatic fibrosis rat models induced by carbon tetrachloride administration in different ways combined with ethanol lavage

目的比较四氯化碳(CCL_4)腹腔注射、皮下注射复合乙醇灌胃SD大鼠制备肝纤维化动物模型,为研究肝纤维化病理机制、治疗提供质量稳定可靠的动物模型。方法 SD大鼠40只随机分为四组,每组10只,腹腔注射造模组用50%CCL_4橄榄油溶液腹腔注射(体积比:四氯化碳:橄榄油=1∶1),剂量0.15mL/100g,2次/周;皮下注射造模组用50%CCL_4橄榄油溶液背部皮下注射,剂量0.3mL/100g,2次/周,两组均在实验第2周开始给大鼠用30%乙醇灌胃,剂量1mL/100g,隔天1次造模。腹腔注射对照组、皮下注射对照组,只采用等量橄榄油腹腔注射、皮下注射,生理盐水灌胃。对比研究CCL_4不同给药途径复合乙醇灌胃建立大鼠肝纤维化模型的效果。结果腹腔注射造模组第8周造模成功,造模结束时死亡3只,死亡率30%,皮下注射造模组第10周造模成功,造模结束时大鼠无死亡,两造模组比较,造模时间比较有显著性差异(P<0.01),肝组织纤维化病理分级无显著性差异(P>0.05)。结论两种方法均可成功建立肝纤维化模型,且各有优势,腹腔注射造模组成模时间短,有时间优势,但是死亡率高,皮下注射造模组成模时间长,死亡率低,有成活优势,可根据实验需求选择应用不同的方法构建动物模型。

Objective To provide reliable hepatic fibrosis rat models for the research on the pathologic mechanism and the treatment of hepatic fibrosis through the comparison of the models induced by gastric administration of ethanol combined with different CCL4 injection ways（intraperitoneally and subcutaneously respectively）.Methods 40 SD rats were randomly divided into 4groups（10rats in each group）：intraperitoneally-injected group,injection of 50%of CCL4 and olive oil（volume ratio,CCL4∶ Olive Oil= 1∶1）at the dosage of 0.15mL/100 g,twice per week;subcutaneously-injected group,injection of 50% of CCL4 and olive oil under the dorsal tissue at the dosage of 0.3mL/100 g,twice per week.Both of the two groups were gastrically administrated with 30% of ethanol every two days at the dosage of 1mL/100 g in the second week of the experiment;the other two control groups were only injected the same amount of olive oil intraperitoneally and subutaneously respectively with gastric administration of normal saline.Then the models prepared by different administration of CCL4 with ethanol were compared.Results Intraperitoneally-injected group was successfully modeled in 8weeks with the death of three rats（the mortality rate was 30%）,while subcutaneously-injected group was modeled in 10 weeks without the death of any rat.There was significant difference in modeling time（P〈0.01）but no significant difference in pathological grading on hepatic fibrosis（P〉0.05）between the two groups.Conclusion Both the two different administration ways of CCL4 could successfully create hepatic fibrosis rat models.Intraperitoneal injection has an advantage in modeling time but its mortality rate is a bit high.However,subcutaneous injection has the advantage in mortality rate but its modeling time is longer.Thus,we could select different CCL4 administration ways according to different experimental purpose.