机构地区:[1]长沙医学院第一临床学院,湖南410219 [2]长沙医学院基础医学院,湖南410219
出 处:《工业卫生与职业病》2023年第2期145-150,共6页Industrial Health and Occupational Diseases
基 金:湖南省自然科学基金项目(2019jj50693);2021年国家级大学生创新创业训练计划(20210823022);2021年国家级大学生创新创业训练计划(202110823010);湖南省大学生创新创业训练计划(S202110823061)。
摘 要:目的探究双酚AF(BPAF)亚急性毒性对小鼠糖脂代谢影响。方法50只SPF级6周龄健康雄性小鼠随机分为5组,对照组、溶液对照组以及100、200和400 mg/kg/d BPAF染毒组,经口染毒14 d,进行葡萄糖耐量试验(OGTT实验),测定小鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL),肝组织切片HE染色以及荧光定量PCR检测过氧化物酶体增殖物激活受体γ(PPAR-γ)、乙酰辅酶A羧化酶1(ACC1)、脂肪酸合成酶(FAS)、磷酸烯醇丙酮酸羧激酶(PERCK)、叉头状转录因子(FoxO1)。结果BPAF染毒组与对照组和溶液对照组比较,BPAF染毒组体质量降低,TG[(3.067±0.581)、(2.896±0.734)、(3.498±0.698)mol/L]比[(2.322±0.303)和(2.284±0.253)mol/L]、TC[(1.052±0.049)、(1.488±0.219)、(1.188±0.192)mol/L]比[(0.645±0.077)和(0.736±0.144)mol/L]含量升高,PPAR-γ、ACC1、FAS、PERCK、FoxO1转录水平升高,且血清内TC、TG含量和肝脏内PPAR-γ、ACC1、FAS、FoxO1、PERCK转录水平与BPAF染毒剂量呈正相关(F=19.971、7.713、45.06、4216.845、399.476、382.564、190.869、156.971,P<0.05)。同时在肝脏切片观察到肝细胞胞质内出现大小不一的脂滴及大量炎细胞浸润;而200、400 mg/(kg·d)剂量组与对照组和溶液对照组比较,肝/体比值、空腹血糖(FBG)[(7.84±1.834)和(8.62±0.73)mol/L]比[(6.36±0.26)和(6.28±0.177)mol/L]水平升高,糖耐量实验中30 min血糖、60 min血糖水平降低,且400 mg/(kg·d)剂量组较200 mg/(kg·d)剂量组明显(F=21.342、9.627、29.91、10.148,P<0.05)。结论亚急性BPAF暴露严重干扰小鼠肝脏脂质代谢及葡萄糖稳态。Objective To investigate the effect of subacute toxicity of bisphenol AF(BPAF)on glycolipid metabolism in mice.Methods A total of 50 SPF male mice aged 6 weeks were randomly divided into five groups:the control group,the solution control group,the 100,200 and 400 mg/kg/d BPAF infection groups.The glucose tolerance test(OGTT experiment)was performed to determine the total serum cholestero(l TC),triglyceride(s TG),low-density lipoprotein(LDL),and high-density lipoprotein(HDL)of the mice.After infected by mouth for 14 days.The morphology of liver tissues were detecetd by HE staining.And the expression levels of the peroxisome proliferation activated receptorγ(PPAR-γ),acetyl-CoA carboxylase 1(ACC1),fatty acid synthase(FAS),phosphoenol pyruvate carboxykinase(PERCK),and fork-tipped transcription facto(r FoxO1)RNAs were detected by fluorescence quantitative PCR.Results Compared with the control group and the solution control group,the body mass significantly reduced in the BPAF infection group,and the levels of TG([3.067±0.581),(2.896±0.734),(3.498±0.698)mol/L]compare([2.322±0.303)and(2.284±0.253)mol/L]and TC([1.052±0.049),(1.488±0.219),(1.188±0.192)mol/L]compare[(0.645±0.077)and(0.736±0.144)mol/L]significantly elevated.In addtion,the PPAR-γ,ACC1,FAS,PERCK,FoxO1 transcriptional levels significantly elevated.Notablely,the intraseral TC,TG,and intrahepatic PPAR-γ,ACC1,FAS,FoxO1,and PERCK transcriptional levels were positively correlated with BPAF doses(F=19.971,7.713,45.06),4216.845、399.476、382.564、190.869、156.971,P<0.05).Additionally,lipid droplets of varying sizes and a large number of inflammatory cell infiltrations were observed in liver slices.The hepatic/body ratio and fasting blood glucose(FBG)[(7.84±1.834)and(8.62±0.73)mol/L]compare[(6.36±0.26)and(6.28±0.177)mol/L]significantly increased in the 200,400 mg/(kg·d)BPAF infection groups,compared with the control group and the solution control group.Furthermore,the blood glucose levels of 30min and 60min in the 400 mg/(kg·d)BPAF infection gr
分 类 号:R114[医药卫生—卫生毒理学]
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