孕期BDE-47暴露对小鼠脂肪因子和胰岛素敏感性的影响

摘要/Abstract

摘要： 目的初步研究孕期四溴联苯醚（2,2′,4,4′-tetrabraomodiphenylether,BDE-47）暴露对母体和仔代小鼠脂肪因子、胰岛素敏感性的影响,并探讨其可能机制。方法雌性C57BL/6小鼠随机分为高、中、低剂量组和对照组,每组5只。适应性饲养1周后与同批健康成年雄鼠合笼,合笼成功后对雌鼠行10 d的BDE-47灌胃,灌胃 1 周后对母鼠行腹腔内注射葡萄糖耐量实验。仔鼠出生后6周时,所有小鼠禁食过夜后处死。酶联免疫吸附实验（enzyme-linked immuno sorbent assay,ELISA）测定母鼠血清胰岛素、瘦素和脂联素水平;实时荧光定量聚合酶链式反应（quantitative real-time PCR,qRT-PCR）和蛋白质印迹法分别检测母鼠和仔代小鼠肝组织中过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor γ,PPARγ）、瘦素和脂联素的mRNA与蛋白表达水平。结果 BDE-47暴露使母鼠葡萄糖代谢紊乱,仔鼠出生后早期发育期间体质量增加,染毒组母鼠及雄性仔鼠肝脏重量及脏器系数较对照组均增大（均P<0.05）。与对照组相比,高剂量组母鼠和雌性仔鼠肝组织中PPARγ的mRNA和蛋白表达降低,高剂量组雄性仔鼠肝组织中PPARγ的mRNA和蛋白表达升高（均P<0.05）;高、中剂量组母鼠瘦素的mRNA和蛋白表达较对照组降低,高剂量组雌性仔鼠瘦素的mRNA表达较其他各组升高,染毒组雄性仔鼠肝组织中瘦素的mRNA表达较对照组降低（均P<0.05）;中剂量组母鼠和雌性仔鼠脂联素的mRNA表达较对照组降低,各剂量组雄性仔鼠肝组织中脂联素的mRNA表达均较对照组降低（均P<0.05）。与雌性仔鼠比较,高剂量组雄性仔鼠的肝脏脏器系数增加、PPARγ的mRNA和蛋白表达升高,中、高剂量组雄性仔鼠瘦素蛋白表达较雌性仔鼠升高,低、高剂量组雄性仔鼠脂联素mRNA的表达较雌性仔鼠降低（P<0.05）。结论 BDE-47使母鼠糖代谢紊乱,使仔代小鼠早期发育期间体质量增加,影响小鼠PPARγ、瘦素和脂联素基因的表达并存在性别差异。

关键词: 2,2',4,4' -四溴联苯醚, 出生结局, 脂肪因子, PPARγ, 性别差异

Abstract: Objective To preliminarily investigate the effects of 2,2',4,4'-tetrabromodiphenyl ether（BDE-47） exposure during pregnancy on adipokines and insulin sensitivity in maternal and offspring mice,explore its possible mechanisms. Methods The female C57BL/6 mice were randomly divided into high,medium,low dose groups and control group,five animals in each group. After being fed for one week,they were caged with healthy adult male mice purchased in the same batch. The female mice were given BDE-47 by intragastric administration for 10 days after successful cage closure. One week after gavage,the maternal mice were treated with glucose tolerance test by intraperitoneal injection. At six weeks after birth,all mice fasted overnight and were killed. The levels of serum insulin,leptin and adiponectin in maternal mice were measured by enzyme-linked immuno sorbent assay（ELISA）. The mRNA and protein expression levels of peroxisome proliferator-activated receptor γ（PPARγ） leptin and adiponectin in the liver tissues of maternal and offspring mice were detected by quantitative real-time PCR（qRT-PCR） and Western blot. Results BDE-47 exposure caused a disturbance of glucose metabolism in maternal mice. The body mass of the offspring mice increased during the early development period after birth,and the liver weight and organ coefficients of the maternal mice and male offspring in the exposure groups were higher than those in the control group（all P<0.05）. Compared with the control group,the mRNA and protein expression of PPARγ in the liver tissue of maternal mice and female offspring in the highdose group decreased,and the mRNA and protein expression of PPARγ in the liver tissue of male offspring in the high dose group increased（all P<0.05）. The mRNA and protein expression of leptin in maternal mice in the high and medium dose groups were lower than those of the control group,the mRNA expression of leptin in female offspring in the high dose group was higher than that of other groups,and the mRNA expression of leptin in the liver tissue of male offsring in the exposure groups was lower than that of the control group（all P<0.05）. The mRNA expression of adiponectin in maternal mice and female offspring in the medium dose group were lower than that of the control group,and the mRNA expression of adiponectin in the liver tissue of male offspring in each dose group were lower than that of the control group（all P<0.05）. Compared with female offspring,the liver organ coefficients of male offspring in the high dose group increased,the mRNA and protein expression of PPARγ increased,the protein expression of leptin in male offspring mice in the medium and high dose groups was higher than that in female offspring mice,and the mRNA expression of adiponectin in male offspring mice in the low and high dose groups was lower than that female offspring mice（all P<0.05）. Conclusion BDE-47 causes glucose metabolism disorder in maternal mice,increases body weight during early development of offspring mice,and affects the expression of PPARγ,leptin and adiponectin genes in mice,and there are gender differences.

Key words: 2,2',4,4'-tetrabromodiphenyl ether, Birth outcome, Adipokines, PPAR γ, Sex difference

中图分类号:

R-332

姜淑瑞, 王嘉穗, 王永治, 王梦林, 祖尼热·吐尔逊, 刘早玲. 孕期BDE-47暴露对小鼠脂肪因子和胰岛素敏感性的影响. [J]职业与健康, 2023, 39(12): 1589-1595.

JIANG Shu-rui, WANG Jia-sui, WANG Yong-zhi, WANG Meng-lin, Zunire·Tuerxun, LIU Zao-ling. Effects of BDE-47 exposure during pregnancy on adipokines and insulin sensitivity in mice. [J]OCCUPATION AND HEALTH, 2023, 39(12): 1589-1595.

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