摘要
目的:槲皮素等植物雌激素早期不当摄入的负面影响已逐渐为人们所关注。本研究以围青春期雌性小鼠为模型,以成年后个体乳腺组织生殖内分泌激素受体表达水平及增殖能力为指标,考察幼年期槲皮素暴露对于乳腺发育的影响。方法:以高效液相色谱四极杆飞行时间串联质谱法检测槲皮素相关代谢产物在血浆及乳腺组织局部分布状况,以免疫组织化学方法检测乳腺上皮细胞内雌、孕激素受体以及增殖相关标志性分子增殖细胞核抗原的表达水平。结果:槲皮素相应代谢产物在乳腺内含量显著高于血浆,存在典型的组织局部富集的现象;在5 mg/(kg·d)剂量下,槲皮素可显著上调乳腺上皮细胞雌激素受体(estrogen receptor,ER)α及ERβ的表达比值,并抑制孕激素受体的表达。结论:乳腺组织对于槲皮素的暴露十分敏感,围青春期槲皮素的不当摄入极有可能通过改变相应激素受体表达谱进而提高个体成年后罹患乳腺相关疾病的风险。
Objective:The negative bioeffects caused by improper dietary intake of some phytoestrogens like quercetin have aroused increasing concerns.The present research used peripubertal female mice as an in vivo model to observe the effect of juvenile exposure to quercetin on breast development as indicated by the expression levels of reproductive endocrine hormone receptors and the proliferative capacity of mammary gland epithelium in adult mice.Methods:The distribution profiles of quercetin metabolites in plasma and partial breast tissue were determined by high performance liquid chromatography-quadrupole-time of flight/mass spectrometry(HPLC-Q-TOF/MS).The expression levels of estrogen(ER)and progesterone(PR)receptors and the proliferation marker proliferating cell nuclear antigen(PCNA)were detected by immunohistochemistry(IHC).Results:The contents of quercetin metabolites in breast tissue were much higher than in plasma,suggesting local accumulation of quercetin metabolites.At a dosage of 5 mg/(kg·d),quercetin dramatically increased estrogen receptor(ER)-αexpression and suppressed ERβand PR expression,thereby increasing ERα/βexpression ratio in mammary gland epithelium.Conclusion:Given local accumulation of quercetin metabolites,breast tissue is very sensitive to quercetin exposure.It seems likely that peripubertal exposure to quercetin obviously alters the profile of reproductive hormone receptor expression in breast tissue during adulthood,thereby rendering the breast more sensitive to carcinogens.
作者
闵佳玲
许春莲
舒翔
邱奇琦
聂少平
谢明勇
胡晓鹃
MIN Jialing;XU Chunlian;SHU Xiang;QIU Qiqi;NIE Shaoping;XIE Mingyong;HU Xiaojuan(State Key Laboratory of Food Science and Technology,Nanchang University,Nanchang 330047,China;Biochemistry and Molecular Biology Department,School of Basic Medical Sciences,Nanchang University,Nanchang 330006,China)
出处
《食品科学》
EI
CAS
CSCD
北大核心
2018年第21期116-121,共6页
Food Science
基金
国家自然科学基金地区科学基金项目(81460468)
江西省青年科学基金项目(20142BAB215044)
中德科学中心项目(GZ731)
