槲皮素通过调节AhR和Nrf2通路对HepG2细胞中药物代谢酶GSTP1的影响  

Effect of quercetin on drug metabolizing enzyme GSTP1 in HepG2 cells by regulating AhR and Nrf2 pathways

作　　者：陈琪 刘婷婷 白图雅 张梦迪[1,2,3] 胡玉霞 李君[1,2,3] 常福厚 CHEN Qi;LIU Ting-ting;BAI Tu-ya;ZHANG Meng-di;HU Yu-xia;LI Jun;CHANG Fu-hou(School of Pharmacy,Inner Mongolia Medical University,Hohhot 010110;New Drug Safety Evaluation Research Center,Hohhot 010110;New Drug Screening Engineering Research Center,Inner Mongolia Autonomous Region,Hohhot 010110)

机构地区：[1]内蒙古医科大学药学院,呼和浩特010110 [2]内蒙古医科大学新药安全评价研究中心,呼和浩特010110 [3]内蒙古自治区新药筛选工程研究中心,呼和浩特010110

出　　处：《中南药学》2022年第1期8-13,共6页Central South Pharmacy

基　　金：国家自然科学基金项目(No.81760676);内蒙古自治区自然科学基金项目(No.2019LH08017);内蒙古自治区高等学校科学研究项目(No.NJZY21593)。

摘　　要：目的探究槲皮素对HepG2细胞中药物代谢酶谷胱甘肽-S-转移酶P1(GSTP1)的影响及其机制。方法将HepG2细胞分为对照组、槲皮素组、Nrf2抑制剂组、槲皮素+Nrf2抑制剂组、AhR抑制剂组、槲皮素+AhR抑制剂组,利用qPCR及Western blot方法检测Nrf2及AhR通路相关标记物NQO1、GSTP1及CYP1A1的表达。同时检测不同浓度槲皮素处理HepG2细胞的Nrf2核易位情况。结果与对照组相比,槲皮素作用于HepG2细胞后,GSTP1、NQO1和CYP1A1 mRNA及NQO1、GSTP1的蛋白表达均升高(P<0.01,P<0.001),但CYP1A1的蛋白表达无显著变化。与槲皮素组相比,加Nrf2抑制剂后GSTP1和NQO1的mRNA和蛋白表达均显著下降(P<0.001),加AhR抑制剂后GSTP1和CYP1A1的mRNA和GSTP1蛋白表达均下降(P<0.001),而CYP1A1的蛋白表达无显著变化,且槲皮素能促进Nrf2核易位。结论槲皮素可激活HepG2中的Nrf2、AhR信号通路进而促进GSTP1的表达,从AhR经典通路下游CYP1A1的表达来判断,槲皮素对AhR通路的激动作用较弱。Objective To determine the effect of quercetin on drug metabolizing enzyme glutathione-S-transferase P1(GSTP1)in HepG2 cells and it mechanism.Methods HepG2 cells were divided into a control group,a quercetin group,an Nrf2 inhibitor group,a quercetin+Nrf2 inhibitor group,an AhR inhibitor group,and a quercetin+AhR inhibitor group.The expressions of Nrf2 and AhR pathway related markers NQO1,GSTP1 and CYP1A1 were detected by qPCR and Western blot.Nuclear translocation of Nrf2 was detected in HepG2 cells treated with quercetin at different concentrations.Results Compared with the control group,after quercetin acted on HepG2 cells,the mRNA of GSTP1,NQO1 and CYP1A1 and the protein expression of NQO1 and GSTP1 increased,but the protein expression of CYP1A1 did not change significantly.Compared with the quercetin group,the mRNA and protein expression of GSTP1 and NQO1 were decreased significantly after adding Nrf2 inhibitor(P<0.001),and the mRNA and protein expression of GSTP1 and CYP1A1 mRNA were decreased after adding AhR inhibitor(P<0.001),but the protein expression of CYP1A1 did not change significantly.And quercetin can promote nuclear translocation of Nrf2.Conclusion Quercetin can activate Nrf2 and AhR signaling pathways in HepG2 and promote the expression of GSTP1.Judging from the expression of CYP1A1 downstream of AhR classical pathway,quercetin has a weak activation effect on AhR pathway.

关 键 词：槲皮素 AHR NRF2 谷胱甘肽-S-转移酶P1 

分 类 号：R285[医药卫生—中药学]