小鼠肝微粒体UGTs诱导活性及扑热息痛代谢研究

目的]以染料木素(Gen)、葡萄糖醛酸内酯(Glu)处理的鼠肝微粒体为体外代谢模型,考察不同条件下尿苷二磷酸葡萄糖醛酸转移酶(UGTs)的活性及其对扑热息痛(APAP)代谢的影响。方法]采用染料木素、葡萄糖醛酸内酯以及2种药物联合对小鼠进行体内诱导,取诱导后小鼠肝脏制备微粒体,构建微粒体体外孵育模型,以4-硝基酚(4-NP)为底物检测UGTs活性,加APAP到孵育体系中反应后再利用HPLC测定其含量。结果]染料木素及2种药物联合诱导后的UGTs比活力分别为(0.553±0.039)和(0.696±0.046)U/mg,对照组和Glu组分别为(0.449±0.017)和(0.457±0.030)U/mg;在加入相同浓度APAP的情况下,Gen组APAP的剩余量低于空白组及Glu组。结论]染料木素可以显著增强UGTs活性和提高APAP代谢效率。

Study on UGTs Activities in Mouse Hepatocyte Microsome and the Metabolism of Paracetamol

Objective] To use the mice liver microsomes induced with genistein and glucurolactone as in vitro metabolic model,study the activity of UDP-glucuronosyl transferases(UGTs) in different conditions and its impact on paracetamol(APAP) metabolism.Method] The mice were induced with genistein,glucurolactone and the mixture of these two medicines(genistein and glucurolactone) in vivo.The liver of induced mice was used to make microsome,and the model of microsomal incubation in vitro was constructed.The enzymatic activity of UGTs was detected using 4-NP as substrate.APAP was added to incubation system,the content of APAP was determined by HPLC after reaction.Result] The activity of UGTs induced with genistein and the mixture of these two medicines were(0.553±0.039) U/mg and(0.696±0.046) U/mg respectively,the activity of UGTs induced with glucurolactone and the control group were(0.456±0.030) U/mg and(0.449±0.017) U/mg respectively;the remaining amount of APAP in Gen group is lower than that in control and Glu group when added with the same concentration of APAP.Conclusion] The genistein could increase the activity of UGTs significantly and improve metabolic efficiency of APAP in vitro.