中文摘要：

目的：采用联合应用低剂量口服和腹腔注射硫代乙酰胺（thioacetamide,TAA）,优化大鼠肝硬化建模方法,并观察二十二碳六烯酸（DHA）抑制肝纤维化的作用.方法：100只雄性SD大鼠随机分为5组：对照组.口服组.腹腔注射组.联合低剂量口服和腹腔注射组及DHA治疗联合组.观察大鼠肝硬化形成率;硬化结节形成及病理观察假小叶形成情况;检测大鼠肝功能指标谷丙氨酸转氨酶（ALT）.内毒素,测定肝组织匀浆过氧化物歧化酶（SOD）和丙二醛（MDA）.结果：口服TAA肝硬化模型组诱导16周后死亡2只（死亡率约为10%）,假小叶的形成率约为85%,癌变1只（癌变率约为5%）.腹腔注射组诱导10周后死亡5只（死亡率约为25%）,假小叶的形成率约为75%.联合组10周后死亡1只（死亡率约为5%）,假小叶的形成率约为90%.联合组毒性反应稍小.3组TAA诱导肝硬化模型大鼠ALT水平及内毒素明显高于正常对照组,而3组TAA肝硬化模型诱导组内未见明显差异.治疗组ALT水平及内毒素明显低于3组TAA肝硬化模型诱导组.治疗组MDA水平明显低于3组TAA肝硬化模型诱导组,SOD水平高于3组TAA肝硬化模型诱导组.结论：肝硬化诱导过程中联合低剂量口服和腹腔注射TAA可成功诱导大鼠肝硬化,DHA可改善联合低剂量口服和腹腔注射TAA诱导肝硬化大鼠的肝功能,抑制肝硬化.

英文摘要：

Objective：To induce liver cirrhosis by combined low-dose oral and intraperitoneally injected thioacetamide method,and further investigate the inhibitory effects of docosahexaenoic acid on liver cirrhosis in rat. Methods：One hundred male SD rats were divided into five groups：control group,oral group,intraperitoneally injected group,combined group and treatment group with DHA. Formation rate of liver cirrhosis was observed. Cirrosis nodule and pathological observation of pseudolobule formation was performed. We detected liver function indexes including alanine aminotransferase （ALT）,endotoxin determination,liver homogenates superoxide dismutase （SOD） and malondialdehyde（MDA）. Results：The toxicity of the combined group is slightly lighter. The mortality in the oral group was 10% （2/20） and cirrhosis rate was 85% （17/20） with one carcinogenesis. Ten weeks after the intraperitoneally injection,the mortality in the oral group was 25% （5/20） and cirrhosis rate was 75% （15/20）. In contrast,the mortality in the combined group was 5% （1/20） and cirrhosis rate was 90% （18/20）. ALT level and endotoxin of three groups with TAA treatment were significantly higher than those of the normal control group,while there was no significant difference among the three groups with TAA treatment. Furthermore,ALT level and endotoxin of rats treated with DHA were lower than those of three groups with TAA treatment. MDA level of the DHA treatment group was significantly lower than that of the three TAA induced cirrhosis groups, while SOD were significantly higher. Conclusion：Combined low-dose oral and intraperitoneally injection of TAA method successfully induced cirrhosis. DHA inhibited liver cirrhosis induced by combined low-dose oral and intraperitoneally injected thioacetamide method in rat.