硫代乙酰胺致大鼠肠源性内毒素血症模型探讨

Study on a rat model of intestinal endotoxemia induced by thioacetamide

目的探讨不同剂量硫代乙酰胺（TAA）所制备的大鼠肠源性内毒素血症（IETM）模型的量效关系。方法将40只大鼠分为4组，每组10只。TAA组分别以200、400、600mg／kg剂量的TAA灌胃，24h后相同剂量TAA重复灌胃一次，建立不同剂量TAA致大鼠IETM的动物模型；健康对照组以等体积0．9％氯化钠溶液灌胃。观察造模后24、48h大鼠死亡情况，48h后采集存活大鼠腹主动脉血，检测血浆内毒素、血清ALT和AST，观察肝组织病理变化。采用单因素方差分析，组间比较采用t检验。结果造模48h后，健康对照组无大鼠死亡，200mg／kgTAA模型组死亡2只，400mg／kgTAA模型组死亡5只，600mg／kgTAA模型组死亡8只。200、400、600mg／kgTAA模型组大鼠血清ALT水平分别为（305．09±116．78）、（901．67±274．31）和（1454．84±473．49）U／L，明显高于健康对照组的（47．81±22．6I）U／L（t=14．583、25．896、20．596，均P〈0．05）；200、400、600mg／kgTAA模型组大鼠血清AST水平分别为（465．88±139．96）、（884．37±250．90）和（1889．23±159．67）U／L，明显高于健康对照组的（69．33±22．04）U／L（t=12．988、18．455、13．542，均P〈0．05）；200、400、600mg／kgTAA模型组大鼠血浆内毒素水平分别为（0．436±0．110）、（0．550土0．095）和（0．620±0．057）Eu／mL，明显高于健康对照组的（0．103±0．056）EU／mL（t=7．335、5．260、8．191，均P〈0．05）。病理学显示不同剂量TAA模型组有不同程度的肝细胞变性坏死。结论TAA剂量为200-600mg／kg时可成功制作IETM模型，200mg／kgTAA模型组大鼠死亡率较低．适于进一步的实验研究。

Objective To investigate the correlation between dose and effect of thioacetamide （TAA） on rat model of intestinal endotoxemia. Methods The models of intestinal endotoxemia were induced by three different doses of TAA by gavage administration of TAA 200, 400, 600 mg/kg respectively once per day for two days. The doses were given at same time point every day. Each group included 10 rats. The rats in the control group were administrated with 2 mL 0. 9%NaC1 saline garage. The death of the rats was observed at 24 hours and 48 hours after administration. The blood samples of the living rats were drawn from abdominal aorta for determining the plasma endotoxin levels, serum alanine aminotransferase （ALT） and aspartated transaminase fAST） levels. The histopathological changes of liver were examined. Single factor analysis of variance was performed and comparision between groups was done using t test. Results No rat in the control group died. Two rats of 200 mg/kg TAA group, five rats of 400 mg/kg TAA group and eight rats of 600 mg/kg TAA group died during the experiment. The mean serum ALT levels of TAA model groups [（305.09 ± 116.78） U/L,（901.67±274.31） U/L, （1454.84±473, 49） U/L] were all significantly higher than that of the control group（47.81±22.61） U/L （t=14. 583, 25. 896 and 20. 596, respectively; all P〈 0.05）. The mean serum AST levels of TAA model groups [-（465.88 ± 139. 96） U/L, （884. 37 ± 250.90） U/L, （1889.23± 159.67） U/L] were all significantly higher than that of the control group （69.33±22.04） U/L （t=12. 988,18. 455 and 13. 542, respectively; all P〈0.05）. The mean plasma endotoxin levels of TAA model groups [-（0. 436±0. 110） EU/mL, （0. 550±0. 095） EU/mL, （0. 620± 0. 057） EU/mL] were all significantly higher than that of the control group （0. 103±0. 056） EU/mL （t= 7. 335, 5. 260 and 8. 191, respectively; all P〈0.05）. The histological results of TAA model groups showed hepatic cell degeneration and necrosis in different degrees. Conclusions TAA with 200- 600 mg/kg is proper to establish the rat model of intestinal endotoxemia. The death rate of rats in the 200 mg/kg TAA group is lower than those of other model groups, which suggests that 200 mg/kg TAA may be the best dosage for establishing rat model for further studies.