三种茶饮料对小鼠肠道首过效应及肝脏Cyp3a、Cyp2e1的影响

摘要/Abstract

摘要： 目的: 研究市售罐装绿茶、冰红茶及茉莉清茶饮料对小鼠肠道首过效应和肝脏细胞色素氧化酶(cytochrome P450,CYP)Cyp3a、Cyp2e1的影响。方法: SPF级小鼠随机分为6组,其中绿茶组、冰红茶组、茉莉清茶组小鼠分别自由饮用绿茶、冰红茶、茉莉清茶 7 d。用血中扑热息痛(acetaminophen,APAP)的浓度推断肠道首过效应。采用差速离心法分离肝/肠微粒体,以Bradford法定量蛋白,紫外分光光度法定量Cyp3a、Cyp2e1及血中APAP浓度。结果: 绿茶组血中APAP浓度较空白组明显升高(P<0.01),而冰红茶组与空白组相比则显著降低(P<0.01);绿茶组和冰红茶组小肠Cyp3a酶活性较空白组显著升高(P<0.05 或P<0.01)。各供试物组肝脏Cyp3a酶活性较空白组明显升高 (P<0.01),各供试物组肝脏Cyp2e1酶活性较空白组显著降低(P<0.01)。结论: 绿茶、冰红茶能显著改变肠道首过效应(绿茶抑制肠道P-gp,诱导肠道Cyp3a;冰红茶则诱导肠道P-gp及肠道Cyp3a;而茉莉清茶对肠道首过效应无影响)。各供试物均诱导肝脏Cyp3a的酶活性,抑制肝脏Cyp2e1的酶活性。故在服用经CYP3A、CYP2E1和P-gp代谢/转运的药物期间,大量或经常饮用上述茶可能影响这些药物的临床疗效和/或不良反应。

关键词: 茶饮料, Cyp3a, Cyp2e1, P-糖蛋白

Abstract: AIM: To investigate the effect of can packaged commercially available green tea, ice black tea and jasmine tea on intestinal first-pass effect and liver Cytochrome P450 (CYPs) Cyp3a, Cyp2e1 activities in mice.METHODS: SPF grade mice were randomly divided into 6 groups, green tea group, ice black tea group, jasmine tea group mice were getting freely access to green tea, ice black tea, jasmine tea respectively for 7 days. Intestinal first-pass effect was inferred through serum acetaminophen (APAP) levels. Liver/intestinal microsomes were prepared by differential centrifugation, and microsomal protein was quantified by Bradford method. Cyp3a, Cyp2e1 activities and serum APAP concentrations were assayed by spectrophotometry.RESULTS: APAP concentrations in green tea group were significantly higher than those in control group (P<0.01), while the levels were notably lower in ice black tea group than those in control group (P<0.01), the intestinal Cyp3a activities in green tea group and ice black tea group were considerably higher than those in control group (P<0.05 or P<0.01). Compared with control group, liver Cyp3a activities in all tea treated groups were greatly increased than those in control group (P<0.01). Compared with control group, liver Cyp2e1 activities in all tea treated groups were obviously reduced (P<0.01).CONCLUSION: Green tea and iced black tea seem significantly change the intestinal first-pass effect (green tea inhibit the activities of intestinal P-gp but induce intestinal Cyp3a, and ice black tea induce both intestinal P-gp and Cyp3a activities), while jasmine tea has no effect on intestinal first-pass effect. All three kinds of tea can significantly induce liver Cyp3a activities and inhibit liver Cyp2e1 activities. Therefore, intensely or frequently consuming these tea beverages during taking the medicines by which are metabolized or transported CYP3A, CYP2E1 and P-gp probably affect the drugs' clinical efficacy.

Key words: Tea beverages, Cyp3a, Cyp2e1, P-glycoprotein

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R965.2

引用本文

林梅, 奇锦峰, 王永辉, 刘建敏, 韩坚. 三种茶饮料对小鼠肠道首过效应及肝脏Cyp3a、Cyp2e1的影响[J]. 中国临床药理学与治疗学, 2011, 16(1): 5-12.

LIN Mei, QI Jin-feng, WANG Yong-hui, LIU Jian-min, HAN Jian. Effects of three kinds of tea beverages on intestinal first-pass effect and liver Cyp3a, Cyp2e1 activities in mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(1): 5-12.

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三种茶饮料对小鼠肠道首过效应及肝脏Cyp3a、Cyp2e1的影响

Effects of three kinds of tea beverages on intestinal first-pass effect and liver Cyp3a, Cyp2e1 activities in mice

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[1]	朱丽, 魏兵, 廖世峨, 张超, 郑晓宇, 刘亚军. 药物代谢酶细胞色素P450单核苷酸多态性影响哮喘儿童吸入皮质醇激素疗效研究[J]. 中国临床药理学与治疗学, 2023, 28(5): 536-543.
[2]	李珊, 柳熠鑫, 任菲菲, 李相晨, 张志清. 天然植物活性成分通过下调 P-糖蛋白逆转肿瘤多药耐药的研究进展[J]. 中国临床药理学与治疗学, 2023, 28(3): 331-340.
[3]	付虹, 田磊. 缺血性脑卒中伴高血压病患者个体化精准治疗的研究[J]. 中国临床药理学与治疗学, 2022, 27(8): 870-876.
[4]	陈思雨陈露露王欣桐李晓晖余鹏欧阳冬生. 药用辅料对CYP3A活性的影响及其对仿制药质量和疗效一致性评价的指导作用[J]. 中国临床药理学与治疗学, 2020, 25(4): 460-466.
[5]	吴懿, 王让让, 王兆文, 樊军卫. 受体SLCO1B1 rs2291075位点多态性对肝移植术后早期他克莫司剂量校正谷浓度的影响[J]. 中国临床药理学与治疗学, 2020, 25(11): 1268-1275.
[6]	刘莉，彭金富，郭成贤，阳喜定，李海刚，阳国平. miR-150对药物代谢酶CYP3A4的调控作用[J]. 中国临床药理学与治疗学, 2018, 23(7): 749-754.
[7]	陈丹，林秀贤，陈尧. CYP2E1调控酒精性肝病发病机制的研究进展[J]. 中国临床药理学与治疗学, 2017, 22(2): 198-203.
[8]	郑琛，孙红，黄旭慧，魏晓霞，屈强，屈健. CYP3A5和MDR1基因多态性对沙格列汀疗效的影响[J]. 中国临床药理学与治疗学, 2016, 21(8): 921-925.
[9]	朱宏平，靳高凤，陈亚军，李新华，张红，黄世博，夏春华，熊玉卿. 柚皮素对K562/A02细胞MDR1 mRNA/P gp的影响及机制研究[J]. 中国临床药理学与治疗学, 2016, 21(11): 1209-1214.
[10]	王寅声, 李晓智, 沈杰, 李絮, 温纯洁, 吴兰香, 周宏灏. 姜黄素对乳腺癌MCF-7与MCF-7/DOX细胞中P-糖蛋白表达的影响及其机制研究[J]. 中国临床药理学与治疗学, 2015, 20(7): 769-774.
[11]	黄伟, 胡晓. 细胞色素P450 3A4 代谢机制有关方面的研究进展[J]. 中国临床药理学与治疗学, 2015, 20(2): 223-229.
[12]	席兰艳，袁洪，明英姿，朱利军，阳国平，谢和宾，黄志军. CYP3A41G、CYP3A53基因多态性对肾移植后高血压患者他克莫司血药浓度/剂量比的影响[J]. 中国临床药理学与治疗学, 2015, 20(12): 1382-1387.
[13]	叶金华，靳高凤，刘名义，朱宏平，陈亚军，冯慧玲，熊玉卿. P-糖蛋白介导阿托伐他汀与阿昔莫司摄取转运的相互作用及其机制研究[J]. 中国临床药理学与治疗学, 2015, 20(12): 1392-1396.
[14]	唐霞, 辛华雯, 李维亮, 欧阳萌. 黄连素对HepG2细胞CYP3A4和P-gp的影响和作用机制研究[J]. 中国临床药理学与治疗学, 2015, 20(1): 7-13.
[15]	欧阳苍鸿, 谢娟. 例心衰患者的MDR1和CYP3A基因多态性与地高辛血药浓度的相关性研究[J]. 中国临床药理学与治疗学, 2014, 19(3): 291-296.