体内外急性酒精性肝损伤模型的研究

Study on Models of Acute Alcoholic Liver Injury in vivo and in vitro

目的:建立体内外急性酒精性肝损伤模型,为进一步研究药物对肝损伤的保护作用奠定基础。方法:测定乙醇的半数致死量,观察不同给药途径不同剂量下血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)活性变化。利用乙醇体外诱导原代培养的肝细胞损伤,检测不同时间和剂量下培养液上清乳酸脱氢酶(LDH)释放量。结果:小鼠灌胃乙醇的半数致死量为9．98 g·kg-1,乙醇灌胃剂量大于6．4 g·kg-1、腹腔注射剂量大于4．0 g·kg-1时,血清ALT、AST有升高趋势。50-400 mmol·L-1乙醇作用于大鼠肝细胞,培养液上清中LDH释放量有增加趋势。结论:体内、体外急性酒精性肝损伤的最适损伤剂量分别为7．2 g·kg-1和50～100 mmol·L-1。

Objective： To establish the acute alcoholic liver injury models （in vivo and in vitro） for further study on protective effects of injured liver by drugs. Method： The half lethal dose of ethanol was measured, the activity change of serum alanine transaminase （ALT） and aspartate transaminase （AST） by alcohols with different doses and administrations were observed. The primary cultured hepatocytes were injured by ethanol,and the cultural superuatants lactic acid dehydrogenase（LDH） release was inspected at different time spots and doses. Result： The half lethal dose for ethanol oral administration in mice was 9. 98 g·kg^-1, Orally and intraperitoneally administered ethanol seemed to increased serum ALT and AST when the doses were higher than 6.4 g· kg^ - 1 and 4.0 g· kg^ - 1 respectively. The LDH in cultural supematants was increased after 50-400 mmol, L· ^-1 ethanol exposure to rat hepatocytes. Conclusion： The optimal injured dose of ethanol in vivo and in vitro were 7.2 g·kg^-1 and 50-100 mmol·L^-1 respectively.