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蒿鳖养阴软坚方通过激活Nrf2/nqo1信号通路抑制肝纤维化发生

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天津医科大学学报 2018年第1期24卷 20-24页

作者：刘悦李杉杉唐诗慧方步武天津医科大学药理学系天津300070

目的:探讨蒿鳖养阴软坚方通过激活Nrf2/nqo1信号通路对四氯化碳复合因素所致大鼠肝纤维化的抑制作用。方法:选用健康Wistar大鼠作为研究对象,将大鼠随机分为正常组、模型组、低剂量组、中剂量组、高剂量组和秋水仙碱组。除正常组大鼠外... 详细信息

目的:探讨蒿鳖养阴软坚方通过激活Nrf2/nqo1信号通路对四氯化碳复合因素所致大鼠肝纤维化的抑制作用。方法:选用健康Wistar大鼠作为研究对象,将大鼠随机分为正常组、模型组、低剂量组、中剂量组、高剂量组和秋水仙碱组。除正常组大鼠外,其余大鼠均给予自制高脂饲料饲养,每周两次皮下注射40%CC14花生油混合溶液,隔日灌胃给予30%乙醇,各给药组每日灌胃给药的同时给予正常组和模型组以等容积的蒸馏水,直至造模时间(共6周)结束后,乌拉坦麻醉大鼠并收集肝组织标本,比色法检测肝组织中羟脯氨酸(Hyp)的含量,免疫组织化学法检测各组大鼠肝组织中Nrf2和nqo1的分布情况,Western blot法检测各组大鼠肝组织中Nrf2和nqo1的表达水平。结果:与正常组相比,模型组Hyp含量明显升高(Pnqo1的表达水平显著升高(Pnqo1通路,上调Nrf2和nqo1的表达,降低肝组织中Hyp的含量,从而发挥抑制由四氯化碳复合因素所致大鼠肝纤维化的作用。

关键词：肝纤维化四氯化碳蒿鳖养阴软坚方羟脯氨酸 Nrf2 nqo1

GSTM1、GYP2E1和nqo1基因多态性与儿童白血病发病风险的初步研究

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中华流行病学杂志 2004年第9期25卷 819-819页

作者：吴玉霞高怡瑾赵金彩金锡鹏夏昭林复旦大学公共卫生学院上海200032 复旦大学附属儿童医院上海市儿童医学中心

儿童白血病发病率近年呈上升趋势,其病因仍不清楚.研究表明毒物代谢酶谷胱甘肽硫转移酶(GSTM1)、细胞色素P4502E1(CYP2E1)和还原型辅酶Ⅰ醌类氧化还原酶(nqo1)的基因多态与多种肿瘤的发生有关,本研究针对GSTM1、CYP2E1和nqo1毒物代谢酶... 详细信息

儿童白血病发病率近年呈上升趋势,其病因仍不清楚.研究表明毒物代谢酶谷胱甘肽硫转移酶(GSTM1)、细胞色素P4502E1(CYP2E1)和还原型辅酶Ⅰ醌类氧化还原酶(nqo1)的基因多态与多种肿瘤的发生有关,本研究针对GSTM1、CYP2E1和nqo1毒物代谢酶基因多态与儿童白血病发病风险进行了初步研究.

关键词： GSTM1 GYP2E1 nqo1 基因多态性儿童白血病发病风险

nqo1、CYP1A1、mEH基因多态性与肺癌易感性关系的病例-对照研究

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癌变．畸变．突变 2001年第4期13卷 266-266页

作者：尹立红林嫔嫔等东南大学公共卫生学院，南京210009 台湾省中山医学院毒理学研究所

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nqo1与肿瘤

国际移植与血液净化杂志 2003年第3期 144-144页

nqo1为体内一种重要的Ⅱ相反应酶,通过去电子还原反应参与机体内外源物质代谢过程.nqo1与醌类物质解毒,抗癌药物生物激活,p53蛋白稳定性调节及TNF-a诱导凋亡效应密切相关,从而在细胞的转化、凋亡及保护中发挥重要作用.其cDNA 609位点上... 详细信息

nqo1为体内一种重要的Ⅱ相反应酶,通过去电子还原反应参与机体内外源物质代谢过程.nqo1与醌类物质解毒,抗癌药物生物激活,p53蛋白稳定性调节及TNF-a诱导凋亡效应密切相关,从而在细胞的转化、凋亡及保护中发挥重要作用.其cDNA 609位点上存在C/T间多态性,使突变型产物发生氨基酸替换,失去酶活性,从而使这一位点多态性与多种肿瘤易感性间存在密切联系.本文着重从以上几方面探讨nqo1与肿瘤间的关系.

关键词： nqo1 化学保护生物激活基因多态性肿瘤

An azo bond primary cleavage and C–C bond secondary cleavage-based polymeric β-lapachone prodrug for selective anti-cancer therapy

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Science China Materials 2025年第2期68卷 640-651页

作者： Weidong Zhao Mengfei Zheng Hongyu Chu Jingxuan Zhang Kun Wang Chenguang Yang Na Shen Zhaohui Tang Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China Department of Gastrointestinal Colorectal and Anal SurgeryChina-Japan Union Hospital of Jilin UniversityChangchun 130033China Department of Pathogenbiology State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious DiseasesCollege of Basic MedicineJilin UniversityChangchun 130062China

β-Lapachone (β-Lap) is a promising orthonaphthoquinone drug for cancer treatment and has been inclinical trials. Its application is constrained by the low aqueoussolubility, and severe side effects. Even prodrug designation isan effective approach to render it with tumor selectivity, it islimited by the lack of modifiable groups on β-Lap. Herein, anovel azo bond primary cleavage and carbon–carbon (C–C)bond secondary cleavage-based polymeric β-Lap prodrug(Azo-Lap NP) is designed, in which the self-immolated paraaminobenzyl linker is connected to poly(L-glutamic acid)(PGlu) via azo linkage and the responsive drug release of β-Lapagainst tumors can be achieved under high NAD(P)H:quinoneoxidoreductase 1 (nqo1) expression and low pH environmentin tumors. The effective covalent loading of β-Lap by Azo-LapNPs permitted a high administration dose of β-Lap and enabled significant tumor retention time. Moreover, Azo-LapNPs markedly reduced the side effects of β-Lap by avoidinghemolysis and the production of methemoglobin. The safety ofAzo-Lap NPs administration is validated in the antitumorexperiment of mice. In the 4T1 model, Azo-Lap NPs exhibiteda markedly higher tumor suppression rate than β-Lap. Thiswork provides an effective and safe polymeric prodrug fortumor selective delivery of β-Lap.

关键词： β-lapachone nqo1 C-C bond cleavage polymeric nanoprodrug azo linkage

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氢醌刺激脐血单个核细胞适应性反应基因表达

中国公共卫生 2009年第11期25卷 1339-1340页

作者：唐深李习艺陆彩玲曾晓春肖德强孙斌郭松超广西医科大学基础医学院免疫学教研室广西南宁530021 广西医科大学公共卫生学院广西医科大学第一附属医院

目的探讨氢醌刺激对脐血单个细胞活性的影响及醌氧化还原酶(nqo1)、热休克蛋白10(HSP10)及巯氧还蛋白过氧化物酶(Prxs)的表达。方法取新鲜脐血分离单个核细胞,10μmol/L氢醌预刺激12 h后,再给予250μmol/L氢醌刺激5 h,磷脂蛋白/溴化丙啶... 详细信息

目的探讨氢醌刺激对脐血单个细胞活性的影响及醌氧化还原酶(nqo1)、热休克蛋白10(HSP10)及巯氧还蛋白过氧化物酶(Prxs)的表达。方法取新鲜脐血分离单个核细胞,10μmol/L氢醌预刺激12 h后,再给予250μmol/L氢醌刺激5 h,磷脂蛋白/溴化丙啶(Anexin V/PI)染色检测细胞活力。荧光定量PCR检测nqo1、HSP10及Prxs的表达。结果脐血单个核细胞受到10μmol/L氢醌预刺激后,可耐受后续250μmol/L氢醌攻击,活细胞数从高剂量组的(44.92±25.10)%提高到(39.37±20.98)%,出现适应性反应。荧光定量PCR结果显示,与空白对照组比较,高剂量组HSP10、Prx3、Prx4表达分别增高(2.22±1.03),(3.44±1.07),(2.97±0.79)倍,适应组Prx1增高(1.08±0.29)倍。nqo1在高剂量组和适应组表达均较空白对照组增高(3.44±1.07)和(3.57±1.31)倍,Prx4在高剂量组表达增高(2.41±0.31)倍,且与适应组比较有明显差别。结论Prx1、Prx3、prx4、HSP10可能参与氢醌诱导的脐血单个核细胞适应性反应。

关键词：氢醌脐血单个核细胞 nqo1 热休克蛋白10(HSP10) 2-CysPrxs 适应性反应

Synthesis and biological evaluation of 8-substituted and deglucuronidated scutellarin and baicalin analogues as antioxidant responsive element activators

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Science China Chemistry 2011年第10期54卷 1565-1575页

作者： YANG Ping KONG XiangZhen CHENG ChangMei LI ChangYan YANG XiaoMing ZHAO Xing'E Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology Ministry of Education Tsinghua University Beijing 100084 China Academy of Military Medical Sciences Beijing 100850 China Jiangsu Simcere Pharmaceutical Research Institute Nanjing 210042 China

Flavonoids are important bioactive dietary compounds, which are proved to be antioxidant responsive element (ARE) activators to defend against electrophilic toxicants and oxidative stress. The activators induce ARE gene transcription through Nrf2 factor, a major transcriptional stimulator of cytoprotective genes, relieved from a Keap1 complex. In this report, based on the structures of two flavonoids, scutellarin and baicalin, which are extracted from two common Chinese plants Dengzhanhua (Erigeron breviscapus (vant) Hand-Mazz) and Huangqin (Scutellaria baicalensis Georigi), respectively, we synthesized several 8-substituted and deglucuronidated analogues and identified the ARE activation effects of these flavonoids. We found that the Baicalin, deglucurnonidated Baicalin and diaza cyclopenta derivative were more active. Their dose-dependent upregulation activities of ARE and nqo1 and induction effects of Nrf2 were testified. The results presented that these three analogues had good upregulation effects on ARE, and they could be potentially utilized in relieving oxidative stress, upon further neuroprotective tests.

关键词： Scutellarin Baicalin ARE activator Nrf2 nqo1

Chemical constituents from the submerged plant Potamogeton crispus and their effects on NAD(P)H:quinone oxidoreductase 1

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Chinese Chemical Letters 2012年第10期23卷 1157-1160页

作者： Miao Ye Jun Zhi Ma Juan Xiong Shu Ting Liu Dong Wang Chong Gang Yuan Ji Yan Ma Jin Feng Hu Department of Natural Products for Chemical Genetic Research Key Laboratory of Brain Functional GenomicsEast China Normal UniversityShanghai 200062China Department of Natural Products Chemistry School of PharmacyFudan UniversityShanghai 201203China School of Life Science East China Normal UniversityShanghai 200062China

A new isopimarane-type diterpene （liwariverol, 1） and eight known compounds were isolated and characterized from the EtOAc extract of the whole plant of Potamogeton crispus. The structure of 1 was elucidated to be 17-hydroxy-8c^H-isopimara-9（11）,15- diene by means of spectroscopic methods. Among the isolates, crenulatoside A （2）, an acyclic sesquiterpene glycoside, was found to have anti-oxidative activity with enhancement of the expression of the NAD（P）H：quinone oxidoreductase 1 （nqo1） in human neuroblastoma SH-SY5Y cells at 100 μmol/L after a 24-h incubation.

关键词： Potamogeton crispus Potamogetonaceae Isopimarane-type diterpene Crenulatoside A nqo1 Anti-oxidative activity

醌氧化还原酶1 C609T基因多态性与大肠癌关系

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中国公共卫生 2010年第4期26卷 415-416页

作者：彭仙娥江荧荧史习舜胡志坚郑霄雁肖景榕林旭福建医科大学公共卫生学院流行病与卫生统计系福州350004 福建省肿瘤医院流行病学办公室福建医科大学分子医学研究中心

目的探讨nqo1基因C609T变异与大肠癌易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）基因分型技术,对268对大肠癌患者和对照者nqo1基因cDNA609位点多态性进行测定。结果病例组中基因型为C/C、C/T、T/T的分别有68,... 详细信息

目的探讨nqo1基因C609T变异与大肠癌易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）基因分型技术,对268对大肠癌患者和对照者nqo1基因cDNA609位点多态性进行测定。结果病例组中基因型为C/C、C/T、T/T的分别有68,149,69例,分别占23.77%,52.10%和24.13%;对照组分别有116,126,44人,占40 56%,44.06%和15.38%;3种基因型频率在2组中分布差异均有统计学意义（P〈0.05）;以C/C基因型作为参照基因型,C/T和T/T2种基因型的调整OR分别为2.06（95%CI=1.37~3.10）和2.64（95%CI=1.57~4.44）;nqo1C609T变异基因型与吸烟、饮用水及食物类型存在交互作用而增加个体患大肠癌的危险。结论携带nqo1C609T,变异基因型个体患大肠癌的风险增加,且该变异基因型与环境因素具有协同致癌作用。

关键词：大肠癌 nqo1 基因多态性病例对照研究