急性肝功能衰竭大鼠内毒素血症的防治研究

Intervention studies of endotoxemia in acute liver failure rats

目的 观察胃肠粘膜保护剂思密达对肝衰竭大鼠内毒素血症的预防作用。方法 SD大鼠65只 ,随机分成3组 ,对照组15只 ,衰竭组25只 ,治疗组25只。衰竭组 :用硫代乙酰胺复制出急性肝衰竭大鼠模型。治疗组 :在肝功能衰竭造模同时应用思密达灌胃 (思密达3g加生理盐水50ml配制 ),每次灌胃2ml,每天2次。对照组 :用生理盐水作对照。3组同时实验 ,第3天剖腹作门静脉内毒素测定及胃肠冲洗液细菌培养 ,并观察胃肠道病理改变。结果 3组大鼠门静脉内毒素水平分别为 :对照组29.33±18.50ng/l;衰竭组105.81±18.82ng/l (较对照组明显升高P<0.01) ;治疗组74.20±21.38ng/l(较衰竭组有明显下降P<0.01)。三组大鼠胃小肠细菌培养结果 :衰竭组较对照组细菌明显增多 (P<0.05) ,治疗组有所下降 ,但无比较意义 (P>0.05) ,胃肠病理改变 :肝功能衰竭组大鼠胃肠扩张明显 ,腔内见大量液体或气体 ,粘膜固有层变薄 ,部分胃粘膜糜烂 ,肝功能衰竭治疗组病变较轻。 结论 由硫代乙酰胺诱导的大鼠急性肝功能衰竭模型门静脉内毒素水平明显增高 ,胃肠道细菌培养提示细菌上移 ,菌落总数明显增多 ,胃肠道存在一定的病变 ,经思密达治疗后 ,门静脉内毒素水平有明显下降 ,细菌总数略有下降 。

Objective To establish an animal model of acute liver failure (ALF) with thioacetamide, and study the effects of smecta (a protectant of gastric mucosa) on preventing endotoxemia. Methods 65 Spague-Dawley rats were used. 15 normal rats served as controls. ALF (n=50) was induced by subcutaneous injection of thioacetamide (300 mg/kg) for consecutive 2 days, 25 of them receiving smecta simultaneously. On the third day, blood endotoxin was detected and alimentary tract was washed to make bacterial cultivation. Results Blood endotoxin was significantly increased in ALF (controls, 29.33±18.5mg/l; ALF, 105.81±18.82mg/l ;p<0.01), and smecta could decrease the elevation (74.70±21.38mg/l vs. 105.81±18.82mg/l, p<0.01). In bacterial cultivation of alimentary tract, a significant increase of CFU was observed in ALF . Smecta also decreased the elevation of bacteria but the difference was not significant . Pathologic study showed the protection of smecta against ALF. Conclusion ALF could be induced by thioacetamide with increased endotoxin level, superior displacement and increase of bacteria. Smecta could reduce these changes and showed protective effects.