基于核因子E2相关因子2/抗氧化反应元件信号通路探讨白黎芦醇对胃癌的化学预防作用及机制研究  

Study on the chemopreventive effect and mechanism of resveratrol on gastric cancer based on nuclear factor erythroid-2-related factor 2/anti-oxidant response element signaling pathway

作　　者：宁灿健 余四旺 NING Can-jian;YU Si-wang(Department of Chemical Biology,Peking University School of Pharmaceutical Sciences,Beijing 100191,China;Department of Molecular and Cellular Pharmacology,Peking University School of Pharmaceutical Sciences,Beijing 100191,China)

机构地区：[1]北京大学药学院化学生物学系,北京100191 [2]北京大学药学院分子与细胞药理学系,北京100191

出　　处：《中国临床药理学杂志》2019年第21期2682-2686,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81472657)

摘　　要：目的基于核因子E2相关因子2(Nrf2)/抗氧化反应元件(ARE)信号通路探讨白藜芦醇(RSV)对胃癌的化学预防作用机制。方法用饲喂含有N-甲基-N5-硝基-亚硝基胍(MNNG)的蒸馏水构建胃癌模型。实验分为空白对照组、模型组、阳性对照组和实验组,每组30只。空白对照组给予等体积的0.9%Na Cl灌胃,模型组给予100.0μg·m L^-1MNNG,阳性对照组给予100.0μg·m L^-1MNNG和12.0 mg·kg-1维A酸片,实验组给予100.0μg·m L^-1MNNG和50 mg·kg-1RSV。4组大鼠均连续给药3个月。用实时荧光定量聚合酶链反应检测大鼠Cyclin D1和PTEN mRNA变化情况,用酶联免疫吸附实验法检测大鼠血浆白细胞介素-6(IL-6)、IL-10和肿瘤坏死因子-α(TNF-α)的表达,用蛋白免疫印迹检测Nrf2、血红素氧化酶1(HO-1)和兔抗醌氧化还原酶1(NQO1)蛋白的表达。结果空白对照组、模型组、阳性对照组和实验组Cyclin D1 mRNA相对表达量分别为(1.02±0.13),(2.24±0.21),(1.48±0.19)和(1.51±0.23),PTEN mRNA相对表达量分别为(0.97±0.15),(0.17±0.04),(0.58±0.11)和(0.61±0.14),模型组的上述指标与空白对照组、实验组、阳性对照组比较,差异均有统计学意义(P<0.001,P<0.05)。空白对照组、模型组、阳性对照组和实验组的TNF-α分别为(24.67±1.24),(52.82±1.46),(25.61±1.31)和(26.09±1.43)ng·m L^-1,IL-6分别为(123.43±5.46),(287.14±5.41),(168.62±5.34)和(167.14±5.24)ng·m L^-1,IL-10分别为(217.61±6.19),(397.81±6.41),(286.43±6.17)和(287.27±6.58)ng·m L^-1,模型组的上述指标均显著高于空白对照组,差异均有统计学意义(均P<0.05)。空白对照组、模型组、阳性对照组和实验组的Nrf2相对表达量分别为(1.02±0.08),(2.67±0.13),(1.43±0.12)和(1.38±0.11),HO-1相对表达量分别为(0.98±0.07),(2.14±0.12),(1.42±0.11)和(1.36±0.13),NQO1相对表达量分别为(0.97±0.09),(1.89±0.11),(1.28±0.11)和(1.25±0.12),模型组的上述指标与空白对照组、实验组、阳性对照组比较,差异�Objective To investigate the chemopreventive effect and mechanism of resveratrol(RSV)on gastric cancer based on nuclear factor erythroid-2-related factor 2/anti-oxidant response element(Nrf2/ARE)signaling pathway.Methods Gastric cancer model was established by feeding distilled water containing N-methyl-N5-nitro-N-nitrosoguanidine(MNNG).The experiment was divided into blank control group,model group,positive control group and experimental group with 30 rats in each group.The blank control group was given equal volume of 0.9%Na Cl by gavage,the model group was given 100.0μg·m L^-1 MNNG,the positive control group was given 100.0μg·m L^-1 MNNG and 12.0 mg·kg-1 retinoic acid tablets,and the experimental group was given 100.0μg·m L^-1 MNNG and 50 mg·kg-1 RSV.4 groups were treated for 3 months.The changes of Cyclin D1 and PTEN mRNA in rats were detected by quantitative real-time polymerase chain reaction.Interleukin-6(IL-6),IL-10 and tumor necrosis factor-α(TNF-α)in rat plasma were detected by enzyme linked immunosorbent assay.The expressions of Nrf2,heme oxygenase 1(HO-1),NAD(P)H:quinine oxidoreductase 1(NQO1)proteins were detected by western blot.Results The relative expressions of Cyclin D1 mRNA in blank control group,model group,positive control group and experimental group were(1.02±0.13),(2.24±0.21),(1.48±0.19)and(1.51±0.23),the relative expressions of PTEN mRNA were(0.97±0.15),(0.17±0.04),(0.58±0.11)and(0.61±0.14),respectively.The differences were statistically significant between model group and blank control,experimental,positive control groups(P<0.001,P<0.05).TNF-αin blank control group,model group,positive control group and experimental group were(24.67±1.24),(52.82±1.46),(25.61±1.31)and(26.09±1.43)ng·m L^-1,IL-6 were(123.43±5.46),(287.14±5.41),(168.62±5.34)and(167.14±5.24)ng·m L^-1,IL-10 were(217.61±6.19),(397.81±6.41),(286.43±6.17)and(287.27±6.58)ng·m L^-1,respectively.TNF-α,IL-6 and IL-10 in the model group were significantly higher than those in the blank control group,

关 键 词：白藜芦醇 核因子E2相关因子2/抗氧化反应元件 胃癌 细胞凋亡 

分 类 号：R28[医药卫生—中药学]