[关键词]
[摘要]
目的 考察甘草提取物对核因子E2相关因子2(Nrf2)信号通路及其下游基因尿苷二磷酸葡糖醛酸转移酶1A1(UGT1A1)、γ谷氨酰半胱胺酸合成酶(γGCS)、多药耐药相关蛋白1(MRP1)和多药耐药相关蛋白2(MRP2)的影响。方法 12只小鼠随机分为对照组和甘草提取物组(150 mg·kg-1)。给药后24 h处死取肝组织,采用qRT-PCR技术检测小鼠肝中Nrf2、UGT1A1、γGCS、MRP1和MRP2 mRNA的表达;Western blot技术测定Nrf2蛋白的表达。结果 与对照组比较,甘草提取物显著诱导了小鼠肝脏中Nrf2 mRNA和蛋白的表达,同时Nrf2下游基因UGT1A1、γGCS、MRP1和MRP2 mRNA的表达也显著提高(均P < 0.05)。结论 甘草提取物诱导了小鼠肝脏中II相解毒酶UGT1A1、γGCS及转运体MRP1、MRP2,其机制可能与上调Nrf2转录因子的表达,激活Nrf2细胞信号转导通路有关。
[Key word]
[Abstract]
Objective To investigate the effects of licorice extract on the expression of mice hepatic nuclear factor E2-related factor 2(Nrf2) and its downstream genes of UDP- glucuronyl transferase 1A1(UGT1A1),gamma glutamyl- cysteine synthase(γGCS),multidrug-resistance associated protein 1(MRP1) and multidrug-resistance associated protein 2(MRP2) in mice. Methods Twelve mice were randomly divided into control group and the licorice extract group(150 mg·kg-1). Mice were sacrificed to take the liver 24 hours after the medication. qRT-PCR was used to measure the expression of Nrf2,UGT1A1,γGCS ,MRP1 and MRP2 mRNA in mice liver. Western blotting methos was used to measure the protein expression of Nrf2. Results Compared to the control group,licorice extract significantly induced mRNA expression of Nrf2,UGT1A1,γGCS,MRP1,MRP2 and the protein expression of Nrf2(P < 0.05). Conclusion Licorice extract induces the expression of phase II detoxifying enzymes UGT1A1 and γGCS as well as transporters MRP1 and MRP2. Its mechanism may be related with the induction of Nrf2 transcription factors and with the activation of Nrf2 cellular signal transduction pathways.
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[基金项目]
国家自然科学基金项目(81202985);中央高校基本科研业务管理费中南大学青年教师助推项目(2012QNZT151)。