三羟异黄酮保护急性酒精性肝损伤机制研究

STUDY ON THE MECHANISM OF GENISTEIN ON PROTECTION AGAINST ALCOHOL-INDUCED ACUTE LIVER INJURY

目的探讨大豆三羟异黄酮(Gen)对急性酒精性肝损伤保护效果及与乙醇代谢相关酶活性的影响关系。方法 2 w龄昆明种小白鼠(90只)随机分为空白对照组,模型组,Gen试剂对照组(200 mg/kg bw),Gen试剂预防组(分别有50、100、200 mg/kg bw的低、中、高三种剂量,乙醇灌胃前给药)和Gen试剂治疗组(低、中、高三种剂量,乙醇灌胃后给药)9组;用50%乙醇12 ml/kg bw大剂量灌胃雄性小鼠诱发急性酒精性肝损伤,实验连续10 d后测定小鼠血液和肝脏组织的丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、丙二醛(MDA)、甘油三酯(TG)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)等生化指标,测定肝脏组织的乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和细胞色素氧化酶系(CYP2E1)的活性。结果模型组小鼠血液与肝脏的ALT、AST水平比较空白对照组和Gen试剂对照组明显升高,差异显著(P<0.05=;Gen预防组与治疗组小鼠血液与肝脏的ALT、AST水平比较模型组显著降低,显示有剂量效应,MDA、TG比较模型组显著降低,GSH、SOD比较模型组显著升高,差异显著(P<0.05);Gen预防组与治疗组小鼠血液与肝脏的ADH、ALDH与模型组比较酶活性显著升高,CYP2E1酶活性显著降低;Gen对照组与空白对照组之间各项检测结果无显著差异。结论 Gen对急性酒精性肝损伤有预防保护效果,有影响乙醇代谢酶活性作用,缓解乙醇代谢产生的氧化应激。

Objective To investigate the effect of protection against alcohol-induced acute liver injury and the impact on the activities of enzymes related to alcohol metabolism by genistein （Gen）. Methods Ninety KM male mice （2 w old） were randomly assigned to 9 groups： control group （untreated）, model group （treated with dosage of 12ml/kg bw of 50% alcohol by intragastric garage （i.g.） to induce acute liver injury）, Gen control group （treated alone with Gen of 200 mg/kg bw）, Gen prevention groups （50, 100 or 200 mg/kg bw of Gen, before treatment with alcohol） and Gen therapy groups （the same three dosages of Gen, after treatment with alcohol）. All groups were administered once daily for 10 consecutive days, then the activities or levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, malondialdehyde （MDA）, triglyceride （TG）, glutathione （GSH） and superoxide dismutase （SOD） were determined in blood and liver, and the activities of alcohol dehydrogenase （ADH）, aldehyde dehydrogenase （ALDH） and CYP2E1 （microsomal ethanol oxidizing system, MEOS） were also assayed in liver. Results Compared with the control and Gen control groups, the activities of AST and ALT in Gen model group in blood and liver were increased significantly （P〈0.05）; the activities of AST and ALT in Gen prevention and therapy groups were lower than that of model group remarkably （P〈 0.05）, and the levels of MDA and TG were lower and the levels of GSH and SOD were higher than those of model group significantly （P〈0.05）. The activities of ADH, ALDH of Gen prevention and therapy groups were increased and CYP2E1 was decreased compared to the control group. There was no significant difference of all indicators between the control and Gen control groups. Conclusion Gen could play the role of protection against alcohol-induced acute liver injury. The mechanism of actions of Gen may be associated with reduced oxidative stress via imnact on the activities of protection against alcohol-induced acute liver injury. The mechanism of actions of Gen may be associated with reducedoxidative stress via impact on the activities of ADH, ALDH and CYP2E1.