【摘要】 奶牛乳腺纤维化对畜牧业造成巨大的经济损失，上皮细胞间充质转化(epithelial-mesenchymal transformation, EMT)过程产生的细胞外基质(extracellular matrix, ECM)引发纤维化表型指标升高，是诱导乳腺纤维化病变的主要原因，因此有效缓解上皮细胞EMT过程是缓解乳腺纤维化的潜在防治手段。玉米黄素(zeaxanthin, ZEA)是一种天然类胡萝卜素，研究表明具有缓解EMT过程的生物学功能，并且具有成本相对低廉的优势，但是ZEA对乳腺纤维化的影响及其潜在作用机制尚缺乏研究。因此本试验的目的是探究ZEA对转化生长因子β1(transforming growth factor-β1,TGF-β1)诱导的小鼠乳腺上皮细胞(mice mammary epithelial cells, mMECs)EMT过程中纤维化表型指标的影响及其潜在机制。试验分为5组，空白对照组、ZEA组、TGF-β1模型组、TGF-β1+ZEA(5μmol/L)组、TGF-β1+ZEA(10μmol/L)组。通过CCK8、Western blot和分子动力学模拟等技术探究ZEA对TGF-β1诱导的mMECs纤维化相关指标的影响。结果显示，ZEA显著缓解了TGF-β1诱导的mMECs的纤维化表型指标的升高，具体表现为，E-cadherin蛋白表达显著升高，Collagen 2、α-SMA和Vimentin蛋白表达显著降低。进一步研究表明，ZEA显著抑制TGF-β1/Smad信号通路的激活。综上所述，ZEA通过抑制TGF-β1/Smad信号通路的激活，抑制纤维化表型指标的升高，从而缓解mMECs细胞的EMT过程。更多还原

【Abstract】 Mammary fibrosis in dairy cows has caused huge economic losses to animal husbandry.The extracellular matrix(ECM) produced by the process of epithelial-mesenchymal transformation(EMT) leads to the increase of fibrosis phenotypic indicators, which is the main reason for inducing mammary fibrosis.Therefore, effectively relieving the EMT process of epithelial cells is a potential means of preventing and treating mammary fibrosis.Zeaxanthin(ZEA) is a natural carotenoid.Studies have shown that it has the biological function of alleviating EMT process and has the advantage of relatively low cost.However, the effect of ZEA on mammary fibrosis and its potential mechanism of action are still lack of research.Therefore, the purpose of this experiment is to explore the effect of ZEA on transforming growth factor β1(TGF-β1),the influence of fibrotic phenotypic indicators in the process of induced mice mammary epithelial cells(mMECs),EMT and its potential mechanism.The cells were divided into 5 groups: blank control group, ZEA group, TGF-β1 model group, TGF-β1+ZEA(5 μmol/L) group, TGF-β1+ZEA(10 μmol/L) group.CCK8,Western blot, and molecular dynamics simulation were used to explore effect of ZEA on TGF-β1 induced mMECs fibrosis phenotypic indicators.The experimental results showed that ZEA significantly alleviated TGF-β1induced elevation of fibrosis phenotypic indicators of mMECs.Specifically,the expression of E-cadherin protein was significantly increased,the expression of collagen2,α-SMA and vimentin proteins was significantly decreased.Further studies showed that ZEA significantly inhibited activation of TGF-β1/Smad signal pathway.In summary,ZEA inhibits the activation of TGF-β1/Smad signaling pathway,inhibits the elevation of fibrosis phenotypic indicators,thus alleviating the EMT process of mMECs cells.更多还原