异甘草素对大鼠急性化学性肝损伤的保护作用

Protective effect of isoliquiritigenin against acute chemical hepatic injury in rats

目的:研究异甘草素(ISL)对CCl4所致大鼠急性化学性肝损伤的保护作用及其机制。方法:①在体实验:选用♂Wistar大鼠48只,随机分6组,每组8只。ISL三剂量给药组分别灌服ISL10,20,40mg·kg-1.d-1;甘草酸二铵胶囊(DG)组灌服DG500mg·kg-1.d-1;正常对照组和模型组每日灌服等容量的溶媒。连续给药7d,qd。以CCl4诱导大鼠急性肝损伤模型,酶学测定各组大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)和超氧化物歧化酶(SOD)活性,以及肝组织丙二醛(MDA)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)含量。②体外实验:采用大鼠离体肝细胞原代培养,并建立CCl4诱导肝细胞损伤模型,检测ISL对其作用的影响。结果:①ISL剂量依赖性降低大鼠血清中升高的ALT和AST活性,升高肝组织中降低的GSH含量、SOD和GSH-Px活性,同时降低过氧化物终产物含量。②ISL浓度(5.0～20.0μmol·L-1)依赖性抑制CCl4引起的ALT和AST升高,ISL20.0μmol·L-1可阻断CCl4产生的肝细胞ALT和AST漏出。结论:ISL对大鼠化学性肝损伤具有显著的保护作用。其机制与清除肝组织中的自由基和抗脂质过氧化等作用有关。

OBJECTIVE To study cytoprotective effect and its mechanisms of isoliquiritigenin（ISL）on chemical liver injury in rats. METHODS The acute hepatic injury model in rats was induced by CC14. Activity of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum and malondialdehyde （MDA）, superoxide dismutase （SOD）,glutathione peroxidase （GSH-Px）, reduced glutathione （GSH） contents in liver tissue were measured In vitro, primary cultured hepatocyte was injured by CC14,and the level of ALT and AST in medium was measured to study protective effect of ISL. RESULTS（1） ISL could decrease the activities of ALT and AST in serum and MDA content in liver tissue, and could be able to increase the levels of SOD.GSH and GSH-Px in liver tissue. （2）After administration of CCh （200. 0μmol·L^-1 ） to the medium, the leakage of ALT and AST increased significantly to a stable level, serving as a good hepatocyte injury model. When hepatocytes was pretreatment with ISL of different concentration （5.0 - 20. 0 mol·L^-1 ） for 48 h prior to CCh exposure, the elevated leakage of ALT and AST induced by CCl4 was dose-dependently reduced. CONCLUSION ISL has protective effect against acute liver injury in rats. This protection is mediated by a decrease in oxidative stress and a concomitant increase in antioxidants.