生姜提取物对苯并芘染毒小鼠Ⅱ相酶的诱导作用及对Nrf2-Keap1通路的影响

doi:10.7506/spkx1002-6630-201819027

食品科学 ›› 2018, Vol. 39 ›› Issue (19): 175-181.doi: 10.7506/spkx1002-6630-201819027

生姜提取物对苯并芘染毒小鼠Ⅱ相酶的诱导作用及对Nrf2-Keap1通路的影响

高增明，马冉冉，刘步云，王永丽*，王斌，李大鹏，李锋*

山东农业大学食品科学与工程学院，山东省高校食品加工技术与质量控制重点实验室，山东泰安 271018

出版日期:2018-10-15 发布日期:2018-10-24
基金资助:
国家自然科学基金青年科学基金项目（31201417）；山东省高等学校科技计划项目（J16LE18）；山东省自然科学基金项目（ZR2018BC063）；山东省“双一流”项目（SYT2017XTTD04）

Induction of Phase II Enzymes by Ginger Extract and Its Effecto n Nrf2-Keap1 Signaling Pathway in Mice Exposed to BαP

GAO Zengming, MA Ranran, LIU Buyun, WANG Yongli*, WANG Bin, LI Dapeng, LI Feng*

Key Laboratory of Food Processing Technology and Quality Control in Shandong Province, College of Food Science and Engineering, Shandong Agricultural University, Tai’an 271018, China

Online:2018-10-15 Published:2018-10-24

摘要/Abstract

摘要： 研究生姜提取物对苯并芘（benzo[α]pyrene，BαP）染毒小鼠抗氧化酶及Ⅱ相酶的影响及调控机制。用100、200、400 mg/（kg?d）的生姜提取物（分别标记为LG、MG和HG）对昆明小鼠连续灌胃给药14 d，然后腹腔注射50 mg/（kg?d） BαP，测定小鼠血清及肝肾中谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）、过氧化氢酶（catalase，CAT）和超氧化物歧化酶（superoxide dismutase，SOD）以及醌氧化还原酶（quinone reductase，QR）、血氧合酶1（hemooxygenase 1，HO-1）和谷胱甘肽-S-转移酶（glutathione-S-transferase，GST）的活力及相应蛋白和mRNA的表达水平，分析了核转录因子E2相关因子2（nuclear factor (erythroid-derived 2)-like 2，Nrf2）和Kelch样环氧氯丙烷相关蛋白1（Kelch like ECH associated protein 1，Keap1）的表达情况。结果表明：与BαP损伤组相比，BαP＋MG和BαP＋HG能显著诱导小鼠血清中CAT和GSH-Px活力及肝肾中CAT、SOD和GSH-Px的活力（P＜0.05）；BαP＋MG和BαP＋HG处理导致动物肝脏中QR、HO-1和GST的活力分别提高了21.7%和29.05%、23.99%和56.39%、32.40%和15.08%。与BαP处理组相比，BαP＋MG极显著提高了Nrf2的蛋白表达水平（21.9%），抑制了Keap1蛋白表达（34.7%）（P＜0.01）。高效液相色谱-轨道离子阱质谱联用方法从生姜提取物中共鉴定出19 种成分。因此，生姜提取物能显著诱导BαP染毒小鼠中抗氧化酶和Ⅱ相酶，并且该过程与Nrf2-Keap1信号通路相关。

关键词: 生姜, 苯并芘, 抗氧化酶, Ⅱ相酶, Nrf2-Keap1

Abstract: The effect of ginger extract on antioxidant and phase II detoxifying enzymes in mice exposed to benzo(α)pyrene (BαP) was investigated and the underlying regulatory mechanism was elucidated. Kunming mice were administered by gavage with ginger extract at 100 (low-dose group, LG), 200 (medium-dose group, MG) and 400 mg/(kg·d) (high-dose group, HG) for 14 consecutive days before intraperitoneal injection with 50 mg/(kg·d) of BαP. Glutathione peroxidase (GSHPx), catalase (CAT), superoxide dismutase (SOD), quinone reductase (QR), hemooxygenase 1 (HO-1) and glutathione-Stransferase (GST) activity and their protein and mRNA expression were analyzed. The expression levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and Kelch like ECH-associated protein 1 (Keap1) were examined as well. Results showed that BαP + MG and BαP + HG significantly (P < 0.05) elevated CAT and GSH-Px activities in the serum and CAT, SOD and GSH-Px activities in the liver and kidney in mice compared to BαP alone. Meanwhile, the administration of BαP + MG and BαP + HG led to a significant increase of QR, HO-1 and GST activity by 21.7%, 23.99% and 32.40% in liver, and by 29.05%, 56.39% and 15.08% in kidney, respectively. In contrast to BαP, BαP + MG treatment led to a 21.9% increase of Nrf2 protein expression and a 34.7% reduction of Keap1 protein expression. Totally, 19 compounds were identified in ginger extract by high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (HPLC/LTQ- Orbitrap-MS). Our results suggest that ginger extract was able to induce antioxidant and phase II enzymes in mice exposed to BαP by a mechanism related to Nrf2-Keap1 signaling pathway.

Key words: ginger, benzo[α]pyrene, antioxidant enzymes, phase II enzymes, Nrf2-Keap1

中图分类号:

TS201.2

高增明，马冉冉，刘步云，王永丽*，王斌，李大鹏，李锋. 生姜提取物对苯并芘染毒小鼠Ⅱ相酶的诱导作用及对Nrf2-Keap1通路的影响[J]. 食品科学, 2018, 39(19): 175-181.

GAO Zengming, MA Ranran, LIU Buyun, WANG Yongli*, WANG Bin, LI Dapeng, LI Feng. Induction of Phase II Enzymes by Ginger Extract and Its Effecto n Nrf2-Keap1 Signaling Pathway in Mice Exposed to BαP[J]. FOOD SCIENCE, 2018, 39(19): 175-181.

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生姜提取物对苯并芘染毒小鼠Ⅱ相酶的诱导作用及对Nrf2-Keap1通路的影响

Induction of Phase II Enzymes by Ginger Extract and Its Effecto n Nrf2-Keap1 Signaling Pathway in Mice Exposed to BαP

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