硫代乙酰胺剂量个体化诱导大鼠肝硬化内毒素血症模型探讨  

Study on the model of liver cirrhosis and endotoxemia in rats induced by thioacetamide

作　　者：张平[1] 焦运[1] 陈虹[1] 袁迎春[1] 于松宁[2] 

机构地区：[1]宁夏医科大学总院疾病感染科,宁夏银川750004 [2]宁夏医科大学总院肝胆外科,宁夏银川750004

出　　处：《中华医院感染学杂志》2015年第20期4627-4629,4635,共4页Chinese Journal of Nosocomiology

基　　金：宁夏自然科学基金资助项目(NZK09142)

摘　　要：目的通过以硫代乙酰胺(TAA)溶液为唯一口服液诱导大鼠肝硬化模型,进一步研究TAA致SD大鼠肝硬化模型血浆内毒素水平,探讨实验性肝硬化内毒素血症大鼠肝组织的表达。方法选择健康雄性SD大鼠80只随机分为3组,第1组(20只)给予清水为饮用水(对照组),第2组(30只)予以0.03%TAA作为饮用水(TTA组),第3组(30只)以0.03%TAA作为初始浓度(剂量个体化TAA组),根据每周体重调整饮用水中TAA浓度,剂量个体化诱导大鼠肝硬化模型、时间12周,进一步将肝硬化模型大鼠及对照组大鼠分为3组:对照组正常+脂多糖(LPS);肝硬化+生理盐水(TAA组);肝硬化+LPS(TAA+LPS组)。结果 TAA固定剂量诱导肝硬化大鼠模型组,大鼠死亡率为26.7%,肝硬化形成率仅53.3%,而采用TAA剂量个体化的第3组大鼠病死率为0,肝硬化形成率90.0%,对照组全部存活;组织学观察HE染色切片光镜下观察显示,肝组织中肝细胞有不同程度的细胞质疏松化和脂肪变性,纤维显著增生,包绕肝细胞团块形成典型的假小叶;第2组大鼠血浆内毒素变化与第1组比较,差异有统计学意义(P<0.01),第3组大鼠血浆内毒素变化与第2组比较,差异无统计学意义。结论根据造模过程中大鼠对TAA反应的个体差异,调整TAA的诱导剂量,该方法可显著降低大鼠病死率,提高肝硬化造模成功率。OBJECTIVE To develop a rat model of liver cirrhosis and endotoxemia induced by thioacetamide （TAA） solution as the only oral solution to further study the plasma endotoxin level in the TAA‐induced rat cirrhosis mod‐el and investigate the expression of liver tissues in experimental liver cirrhosis conditions .METHODS Totally 80 healthy male SD rats were selected and randomly divided into three groups .Group 1 （20 rats） received clear water to drink as the control group ,group 2 （TTA group ,30 rats） used 0 .03% TAA as the drinking water .Group 3 （individual dosed group ,30 rats） used 0 .03% TAA as the initial concentration and the TAA concentration in drinking water was adjusted each week according to the weight and the liver cirrhosis model was induced by indi‐vidual dosage for 12 weeks .The rat models of liver cirrhosis and healthy rats were further divided into three groups：normal＋LPS （LPS group） ,liver cirrhosis＋saline （TAA group） ,and liver cirrhosis＋LPS （TAA＋LPS group） .RESULTS In the rat model of group 2 ,mortality was 26 .7% and the cirrhosis formation rate was only 53 .3% .In group 3 ,mortality was 0 ,the cirrhosis formation rate was 90 .0% .All rats survived in the control group .The histological observation of HE stained sections under light microscope showed different degrees of loosen cytoplasm and fatty degeneration in liver cells ,significant fibroplasia and typical pseudolobuli around the liver cell mass .There was significant difference in changes of plasma endotoxin level between group 2 and group 1 （P〈0 .01） ,while the difference was not significant in changes of plasma endotoxin level between group 3 and group 2 .CONCLUSION Adjustment of TAA induction dose according to individual differences in reaction to TAA during the process of modeling can significantly reduce mortality in rats and improve the success of modeling .

关 键 词：硫代乙酰胺 剂量个体化诱导 肝硬化内毒素血症 

分 类 号：R446[医药卫生—诊断学]