高脂日粮对初情期小鼠乳腺发育的影响及分子机制

【目的】研究高脂日粮对初情期小鼠乳腺发育的影响及可能机制。【方法】选用20只4周龄昆明雌性小鼠,设对照组和高脂日粮组,试验期4周,每周称体质量并统计采食量。试验结束后采集小鼠乳腺并称质量,采用wholemount及HE染色观察小鼠乳腺组织形态结构及导管数量。利用Western blot检测初情期小鼠乳腺组织胰岛素样生长因子1(Insulin-like growth factor1,IGF-1)、增殖相关信号通路关键蛋白蛋白激酶B(Protein kinase B,Akt)、胞外调控的蛋白激酶(Extracellular regulated protein kinase,Er K)以及炎症信号通路关键蛋白Toll样受体4(Toll-like receptor 4,TLR4)、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)和核因子κB激酶抑制剂(Inhibitor of nuclear factor kappa-B kinase,IKK)的表达。【结果】高脂日粮组小鼠采食量极显著低于对照组(P0.01),但在能量摄入方面与对照组无显著差异。高脂日粮组小鼠的体质量增加显著高于对照组(P0.05)。高脂日粮组小鼠在乳腺质量、乳腺质量与体质量的比值上均极显著高于对照组(P0.01)。乳腺组织的whole-mount及HE染色结果表明,高脂日粮组小鼠乳腺导管发育明显被抑制,其乳腺组织的导管数和密度明显降低,乳腺组织的终末乳芽数量也极显著低于对照组(P0.01)。高脂日粮能够显著抑制小鼠乳腺组织IGF-I的蛋白表达以及Akt、Erk和IKK的磷酸化水平(P0.01或0.05),极显著促进小鼠乳腺组织TLR4的蛋白表达(P0.01)和显著促进JNK的磷酸化水平(P0.05)。【结论】高脂日粮能够抑制初情期小鼠乳腺发育,这可能是通过抑制乳腺增殖的相关信号和促进乳腺组织炎症的相关信号来实现。

Effect of high-fat diet on mammary gland development of pubertal mice and the molecular mechanism

Objective] To investigate the effect of high-fat diet (HFD) on mammary gland development of pubertal mice and explore the possible underlying mechanisms.Method] Twenty 4-week-old Kunming female mice were randomly divided into control group and HFD group.The trial lasted for four weeks.The body weight and feed intake were recorded weekly.At the end of the trial, mammary glands were collected and weighed.The morphology and number of ducts were observed by using whole-mount and HE staining.Western blot was used to analyze the expressions of insulin-like growth factor 1 (IGF-1), proliferation related signaling pathway proteins such as protein kinase B (Akt) and extracellular regulated protein kinases (ErK), as well as inflammation related signaling pathway proteins, including toll-like receptor 4 (TLR4), c-Jun N-terminal kinase (JNK) and inhibitor of nuclear factor kappa-B kinase (IKK) in the mammary glands.Result] The feed intake of the HFD group was significantly lower than that of control group(P<0.05), There was no significant difference in energy intakes between two groups.The body weight gain of HFD group was significantly higher than that of control group (P<0.05).In addition, HFD significantly increased mammary gland weight and the ratio of mammary gland weight to body weight (P<0.01).The results of whole-mount and HE staining demonstrated that the mammary gland development of HFD group mice were markedly inhibited, with significantly decreased duct number, duct density and number of terminal end buds (P<0.01).HFD significantly inhibited IGF-1 expression and the phosphorylation of Akt, Erk and IKK in mammary glands (P<0.01 or 0.05), while significantly promoted TLR4 expression (P<0.01) and JNK phosphorylation (P<0.05).Conclusion] HFD can suppress mammary gland development of pubertal mice, which might result from the inhibiton of proliferative signals and stimulation of inflammatory signals.