硫代乙酰胺致大鼠肝性脑病模型的量-效关系

Dose-effect of Thioacetamide on Animal Model of Hepatic Encephalopathy in Rats

目的 :探讨不同剂量硫代乙酰胺 (TAA)致大鼠肝性脑病 /轻微型肝性脑病 (HE/MHE)的量 -效关系。方法 :设立 3个TAA剂量组 ,分别以 2 0 0、2 5 0、35 0mg/(kg·d)剂量的TAA隔日行腹腔内注射 ,共 2次 ,建立不同剂量TAA致大鼠肝性脑病的动物模型 ,1d后进行检测脑干听觉诱发电位 (BAEP)和门静脉血浆内毒素 ,血氨 ,肝功能 ,肝脏病理等指标。结果 :不同剂量TAA组的大鼠在HE/MHE发生率 ,肝性脑病分级评分 ,内毒素 ,血氨 ,肝功能和肝脏病理变化等方面均差异显著 (P <0 .0 5 ) ,TAA剂量越大 ,内毒素和血氨水平越高 ,肝功能损害和肝脏病理变化越明显 ,HE/MHE发生率和肝性脑病分级评分越高 ,存在明显的量 -效关系。结论 :TAA致大鼠肝性脑病模型具有显著的量效关系 ,其中 2 0 0mg/(kg·d)剂量TAA为制备MHE模型的适宜剂量。

Objective:To investigate the correlation between dose and effect of thioacetamide (TAA) on animal model of hepatic encephalopathy in rats. Methods: Animal models of hepatic encephalopathy were induced by three different doses of TAA by two intraperitoneal injections of TAA 200mg/kg, 250mg/kg, 350mg/kg of body weight respectively at 48 h intervals (n=12). Brainstem auditory evoked potentials (BAEP) and plasma endotoxin from portal vein of rats, serum ammonia, serum liver function and pathology of liver were examined. Results: There were significant differences among three different TAA dose groups in rats on incidences of HE/MHE, grades of HE, plasma endotoxin, serum ammonia,serum liver function and changes of liver pathology(P<0.05).Conclusion: There were significantly differences on animal model of hepatic encephalopathy induced by different dose of TAA in rats, which showed significant correlation between dose and effect. Two intraperitoneal injections of TAA (200mg/kg body weight) at 48hour intervals is ideal method of MHE model.