柚皮素及其结构修饰产物拮抗APAP所致的L02肝细胞损伤

目的:探讨以柚皮素(C_(15)H_(12)O_(5))为母核进行结构修饰改造的系列化合物对对乙酰氨基酚(acetaminophen,APAP)诱导的L02肝细胞损伤的预防和治疗作用。方法:设立溶剂对照组、APAP模型组、APAP+化合物组和化合物自身对照组,用CCK-8法检测细胞的存活率。通过存活率的高低,比较不同化合物对APAP诱导的L02肝细胞损伤的影响。结果:化合物预给药结果显示,与APAP模型组相比,25μmol/L的化合物3,4,5,6,7,8可显著提高细胞存活率(p<0.05),而化合物1(柚皮素)和化合物2(柚皮苷)组细胞存活率无显著变化(p>0.05)。化合物后给药结果显示,与APAP模型组相比,25μmol/L的化合物3,4,5,6,7,8可显著提高细胞存活率(p<0.05),而柚皮素和柚皮苷组细胞存活率无显著变化(p>0.05)。化合物保肝活性剂量依赖性实验结果显示,与模型组(APAP)相比,化合物3、8的5μM、10μM、25μM浓度组、化合物4、5的10、25μM浓度组和化合物6、7的25μM、50μM、100μM浓度组的细胞存活率均显著提高(p<0.05)。结论:本研究中,柚皮素结构修饰产物化合物对APAP诱导的肝细胞损伤不管是损伤前预给药,还是损伤后给药均具有拮抗作用,且其拮抗作用具有剂量依赖性。实验结果表明柚皮素经过结构改造后,其修饰产物保护肝细胞的作用明显提高。

Protective Effects of Naringenin and its Modified Products Against APAP-induced Injury in L02 Hepatocytes

Objective:To investigate the preventive and therapeutic effects of a series of structural-modified products with Naringenin(C₁₅H₁₂O₅)on Acetaminophen(APAP)induced L02 injury.Methods:Cells were divided into vehicle control group,APAP group,APAP+compound group and compound group.And the cell survival rate was measured by CCK-8.The effects of different compounds on APAP-induced L02 injury were compared by the survival rate.Results:In pre-treatment with compounds study,compared with APAP group,compound 3,4,5,6,7,8 with 25μM increased cell survival rate significantly(p<0.05),while naringenin and naringin showed no significant change(p>0.05).The same results were obtained in post-treatment with compounds study.The results of concentration dependent experiments showed that the survival rate of compound 3 and 8 with concentration of 5μM,10μM and 25μM were significantly higher than that of the model group(p<0.05);and the same results were obtained in the following groups:compound 4,5 with 10μM and 25μM concentration groups,compound 6,7 with 25μM,50μM and 100μM concentration groups.Results:In this study,the structural modified products of naringenin have protective effect against APAP-induced hepatocyte injury both before and after the injury,and the protective effect was dose-dependent.In a word,the protective effect of naringenin structural modified products on hepatocytes was significantly enhanced comparing with naringenin.