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为探究雌激素对雌鱼体内脂肪代谢的影响,研究分别使用50和250μg/L的来曲唑(Letrozole、LET)与他莫昔芬(Tamoxifen、TAM)两种抗雌激素药物,构建了雌性斑马鱼(Danio rerio)雌激素缺乏模型和雌激素受体竞争抑制模型,并检测两种药物处理后斑马鱼肝脏、内脏和肌肉的甘油三酯(TG)含量变化以及肝脏内雌激素和脂肪代谢相关基因的变化。结果显示,低浓度LET处理后雌鱼肝脏和内脏TG显著上升(P<0.05);高浓度TAM处理后肝脏TG含量显著降低(P<0.05),其他各组处理TG均无差异。基因m RNA检测结果表明,两种浓度LET和TAM处理的雌性斑马鱼芳香化酶(CYP19A)表达均显著下调(P<0.05),低浓度TAM暴露导致雌激素受体(ERα)表达显著下调(P<0.05)。此外,两种浓度LET处理均引起了脂肪酸合成酶(FAS)表达显著上调,微粒体的TG转运蛋白(MTP)表达显著下调(P<0.05);低浓度TAM引起了MTP表达显著下调(P<0.05),而高浓度TAM组则引起了MTP表达显著上调(P<0.05)。综合各相关指标,研究结果表明雌激素确实在雌性斑马鱼脂肪代谢中发挥作用,然而不同程度和方式的雌激素抑制会导致不同的脂代谢失调表现,这提示鱼体内雌激素紊乱所导致的脂代谢失调与雌激素浓度和作用通路上的受阻位点有关,并受到多重因子参与的内分泌调控网络的调节。
In order to explore the effects of estrogen on fat metabolism in female fish, two antiestrogenic drugs, letrozole (LET) and tamoxifen (TAM), were used to establish female Danio rerio model of estrogen deficiency and estrogen receptor competition inhibition model, and detect the changes of triglyceride (TG) content in liver, viscera and muscle of zebrafish after treatment with two drugs, and the changes of estrogen and fat metabolism Related gene changes. The results showed that liver and visceral TG increased significantly (P <0.05) in low concentration LET treatment group, but decreased in high concentration TAM group (P <0.05). The result of gene m RNA showed that the expression of CYP19A in two concentrations of LET and TAM was significantly decreased (P <0.05), and the expression of estrogen receptor (ERα) was significantly downregulated in low concentration of TAM P <0.05). In addition, both LET treatment resulted in significant up-regulation of fatty acid synthase (FAS) expression and microsomal TG transporter (MTP) expression (P <0.05); low concentration of TAM caused a significant down-regulation of MTP expression (P < 0.05), while the high concentration of TAM group caused a significant up-regulation of MTP expression (P <0.05). Based on the relevant indicators, the results show that estrogen does play a role in the fat metabolism of female zebrafish, but different degrees and ways of estrogen inhibition lead to different dyslipidemic performance, suggesting that fat in fish caused by estrogen imbalance Metabolic imbalances are related to the concentration of estrogen and the blocked sites on the pathway, and are regulated by endocrine regulatory networks involved in multiple factors.