TAA诱导大鼠肝硬化模型及内毒素血症在肝硬化中作用的探讨

A Study on Thioacetamide-induced Rat Model of Liver Cirrhosis and the Effect of Endotoxin in the Development of Cirrhosis

目的:建立稳定高效的硫代乙酰胺(thioacetamide,TAA)大鼠肝纤维化模型,探讨TAA诱导大鼠肝纤维化模型最佳初始浓度,观察大鼠肝纤维化模型建立成功后肝脏病理、血清ALT、内毒素变化。方法:SD雄性大鼠30只,随机分为两组,对照组15只、TAA组15只,对照组只给予饮用水,TAA组前6周在饮用水中加入0.03%TAA、后6周在饮用水中加入0.04%TAA造模,共12周。结果:TAA组肝硬化形成率95.8%,病死率4.2%;TAA组光镜下见正常肝小叶结构消失,形成大小不等的假小叶;TAA组血浆ALT水平及内毒素明显高于对照组,差异有统计学意义(P<0.05)。结论:口服0.03%TAA作为诱导剂量,可成功诱导大鼠肝硬化,且肝硬化形成率高,该剂量大鼠死亡率低;且说明内毒素血症与大鼠肝硬化有一定关系。

Objective： To establish the stable and efficient rat hepatic fibrosis model induced by Thioacetamide （TAA）, study the best＇ does of TAA and to observe the pathology and function of liver, changes in alanineaminotransferase（ALT） and en- dotoxin. Methods： 30 SD male rats were selected and randomly divided into 2 groups, the control group（15） and the model group （15）. The control group was treated with only water and the model group was treated with 0.03 % TAA（first six weeks） and 0.04 % TAA （latter six weeks）. After twelve weeks, all rats were executed and made into hepaticsmears. Results： Mortality in the model group was 4.17 % and the rate of hepatic fibrosis was 95.83 %. Through the Light microscope, the normal lobular structure was found disappeared and the false lobules formed. The content levels of serum ALT and serum endotoxin in the plasma of model group were higher than those in the control group. Conclusion： 0.03 % TAA - induced cirrhosis showed a low mortality and high success rate, and that endotoxin can accelerate liver fibrosis and the formation of cirrhosis.