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大豆黄酮影响青春期小鼠乳腺发育的潜在机制OACSTPCD

Underlying mechanism of daidzein on mammary gland development in adolescent mice

中文摘要英文摘要

[目的]以大豆黄酮(DZ)作用于青春期雌性小鼠,探讨其通过上调雌二醇(E2)水平和雌激素受体β(ERβ)受体表达影响青春期小鼠乳腺发育的机制,为DZ及其他植物雌激素类在畜牧生产和临床应用提供依据.[方法]选取 48 只 2 周龄C57BL/6 雌性小鼠,随机均分为 3 组:对照组,腹腔注射无菌的PBS;DZ处理组,腹腔注射DZ(100 mg·kg-1);阳性对照组,腹腔注射E2(0.2 mg·kg-1),每组16 只.分别在饲养至21 和28 d,每组随机选取8 只,采集血液,测定血液中E2 含量,处死后摘取乳腺,测定乳腺指数并检测乳腺组织中E2 含量.取同侧部位乳腺制作组织学切片,免疫组化检测核增殖抗原蛋白(PCNA)的表达,Western blot法分析乳腺组织内细胞周期蛋白D1(cyclin D1)和D3(cyclin D3)、ERβ蛋白表达水平.[结果]与对照组相比,DZ处理显著增加饲养21~28 d小鼠体重及采食量;增加21d小鼠血液和乳腺组织中E2 含量,但未达到显著水平(P>0.05);显著增加 28d小鼠血液和乳腺组织中E2 含量(P<0.05);E2 处理血液中E2 含量均极显著增加.DZ处理对饲养 21d小鼠乳腺指数影响较小,显著增加饲养 28d小鼠乳腺指数(P<0.05);E2 处理具有相同趋势(P<0.05).HE染色结果显示,DZ和E2 处理均极显著增加饲养 21 和 28d小鼠乳腺组织小叶内的导管数(P<0.01)和乳腺组织PCNA阳性细胞数(P<0.01).Western blot结果显示,DZ及E2 处理均可上调小鼠乳腺组织cyclinD1、cyclinB1、ERβ蛋白的表达,显著上调饲养 28d小鼠cyclinD1、cyclinB1、ERβ蛋白的表达(P<0.05).[结论]DZ处理可促进青春期小鼠乳腺发育,促进乳腺细胞增殖和分裂,这种作用可能与内源性E2 水平升高及ERβ受体有关.

[Objectives]The phytoestrogen daidzein(DZ)was used to act on adolescent mice to investigate its effects on mammary development by increasing 1,7-β-estradiol(E2)level and upregulating estrogen receptor β(ERβ)expression,providing a basis for DZ and other phytoestrogens in animal production and clinical application.[Methods]Forty-eight 2-week-old female C57BL/6 mices randomly divided into 3 groups:control group,intraperitoneal injection of sterile PBS;DZ group,intraperitoneal injection of DZ(100 mg·kg-1·d-1);positive control group,intraperitoneal injection of E2(0.2 mg·kg-1·d-1).On the 21 and 28 day,8 mices from each group were randomly selected and their blood was collected,the content of E2 in the blood was measured on the basis of group.After death,the mammary glands were immediately isolated and weighed to measure the index of mammary glands and detect the content of E2 in mammary tissues.The expression of proliferating cell nuclear antigen(PCNA)protein was detected by immunohistochemistry.Cell cycle-related protein and estrogen receptor β(ERβ)protein expression levels were analyzed by Western blot.[Results]Compared with the control group,DZ treatment significantly increased the body weight and daily feed intake of mice on the 21 and 28 day,increased E2 levels in blood and breast tissues of mice on the 21 day,but not significantly(P>0.05)and significantly increased them on the 28 day(P<0.05).Similarly,E2 treatment also significantly increased the content of E2 in blood.DZ treatment had little effect on the mammary index of mice on the 21 day,but significantly increased the index on the 28 day(P<0.05);E2 treatment had the same trend(P<0.05).HE staining showed that DZ and E2 treatments significantly increased the numbers of ducts and PCNA positive cells in breast tissues of mice on the 21 and 28 day(P<0.01).Western blot results showed that DZ and E2 treatments up-regulated the protein expressions of cyclinD1,cyclinB1 and ERβ in breast tissues of mice,and specially significantly up-regulated the protein expressions of cyclinD1,cyclinB1 and ERβ on the 28 day(P<0.05).[Conclutions]Phytoestrogen DZ could promote the development of mammary gland of adolescent mice,and promote the proliferation and division of mammary cells,which might be related to the increase of endogenous E2 level and ERβ receptor.

谢娜娜;黄心河;张亚锋;张源淑;韩正康

南京农业大学动物医学院/农业农村部动物生理生化重点开放实验室,江苏 南京 210095

畜牧业

大豆黄酮(DZ)雌二醇(E2)青春期小鼠乳腺发育细胞周期

daidzein(DZ)1,7-β-estradiol(E2)adolescent micemammary developmentcell cycle

《南京农业大学学报》 2024 (001)

血管紧张素转化酶2(ACE2)对SARA诱发山羊乳腺炎的抗损伤机制及联合间充质干细胞(MSCs)的靶向治疗作用

36-43 / 8

国家自然科学基金项目(31972640)

10.7685/jnau.202208038

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