机构地区:[1]新疆医科大学公共卫生学院,新疆乌鲁木齐830011
出 处:《毒理学杂志》2021年第1期20-23,29,共5页Journal of Toxicology
基 金:国家自然科学基金(81760596);新疆维吾尔自治区自然科学基金(2019D01C209)。
摘 要:目的研究2,2′,4,4′,5,5′-六溴联苯醚(2,2′,4,4′,5,5′-Hexabromodiphenyl ether,BDE-153)对C57BL/6小鼠胰岛素抵抗和脂肪因子的影响,并初步探讨其可能的机制。方法雄性C57BL/6小鼠随机分为对照组、BDE-153染毒高、中和低剂量组。利用腹腔注射葡萄糖耐量实验(IPGTT)评估BDE-153对小鼠葡萄糖耐量的影响,以荧光定量PCR和Western blot检测小鼠脂肪组织中瘦素、脂联素和过氧化物酶体增殖子激活受体γ(PPARγ)基因的mRNA表达水平和蛋白表达水平。结果高、中、低剂量组肝脏器系数均高于对照组,高剂量组肝脏脏器系数高于低剂量组(P<0.05)。与对照组相比,BDE-153染毒组小鼠各时点均出现血糖降低趋势,各组小鼠血糖总曲线下面积(GAUC)比较,高、中和低剂量组GAUC均小于对照组(P<0.05)。高剂量组瘦素基因的mRNA表达和蛋白表达高于对照组和低剂量组(P<0.05)。高剂量组PPARγ基因的mRNA表达高于对照组和低剂量组,高剂量组和中剂量组PPARγ基因的蛋白表达高于对照组,高剂量组的PPARγ蛋白表达高于低剂量组(P<0.05)。高剂量组的脂联素基因mRNA表达低于对照组和低剂量组(P<0.05)。结论BDE-153暴露可引起小鼠瘦素和PPARγ基因的mRNA表达和蛋白表达升高,脂联素基因的mRNA表达降低,这可能是BDE-153调节脂肪细胞分泌脂肪因子和影响胰岛素敏感性的机制之一。Objective To investigate the effects and possible mechanism of 2,2′,4,4′,5,5′-hexabromodiphenyl ether(BDE-153)on insulin resistance and adipokines in C57 BL/6 mice.Methods Male C57 BL/6 mice were randomly divided into control group,BDE-153 high-dose group,BDE-153 medium-dose group,and BDE-153 low-dose group.Intraperitoneal glucose tolerance test(IPGTT)was used to evaluate the effect of BDE-153 on glucose tolerance in mice.The mRNA and protein expression levels of leptin,adiponectin and PPARγgenes in adipose tissue of mice were determined by real-time quantitative PCR and Western blot.Results The liver organ coefficients of the high,medium and low dose groups were higher than those of the control group,and the liver organ coefficients of the high dose group were higher than that of the low dose group(P<0.05).Compared with the control group,the mice showed a trend of decreasing blood glucose at all time points in each BDE-153-exposed group.Area under the total blood glucose curve(GAUC)was lower in the high-dose,medium-dose,and low-dose groups than in the control group(P<0.05).The mRNA and protein expressions of leptin gene in the high-dose group were higher than those in the control group and the low-dose group(P<0.05).The mRNA expressions of PPARγ gene in the high-dose group were higher than that in the control group and the low-dose group,the protein expressions of the PPARγ gene in the high-dose group and the middle-dose group were higher than that in the control group,and the protein expression of PPARγ in the high-dose group was higher than that in the low-dose group(P<0.05).The mRNA expressions of adiponectin gene in the high-dose group were lower than that in the control group and the low-dose group(P<0.05).Conclusion Exposure to BDE-153 can increase the mRNA and protein expressions of leptin and PPARγgenes in mice,and decrease the mRNA expressions of adiponectin gene,which may be one of the mechanisms by which BDE-153 regulates adipocyte secretion of adipokines and affects insulin sensitivity.
分 类 号:R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]
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