全氟辛酸对大鼠肝脏氧化应激与PPARα及其所调控的CYP4A1基因表达的影响

发布时间：2018-05-19 13:16

本文选题：全氟辛酸 + 氧化应激　；参考：《卫生研究》2017年05期

【摘要】：目的研究全氟辛酸(perfluorooctanoic acid,PFOA)致大鼠肝脏氧化应激以及对过氧化物酶体增殖剂激活受体(PPAR)α、细胞色素P450(CYP)4A1基因以及PPARα蛋白表达的影响。方法将28只雄性SD大鼠随机分为4组,每组7只,分别为对照组(双蒸水)、低剂量组[PFOA 1 mg/(kg·d)]、中剂量组[PFOA 5 mg/(kg·d)]和高剂量组[PFOA 25 mg/(kg·d)],连续14 d经口灌胃后处死,称重肝脏并计算肝脏系数。用生化检测试剂盒测定大鼠肝脏组织总超氧化物歧化酶(T-SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性以及丙二醛(MDA)含量;荧光定量PCR检测PPARα及CYP4A1基因的mRNA转录水平;Western blot检测PPARα蛋白表达水平。结果从灌胃第5天开始,高剂量组体重与对照组差异有统计学意义(P0.05)。中、高剂量组肝脏重量和肝脏系数与对照组相比,均显著升高(P0.05)。低剂量组大鼠肝脏SOD和GSH-Px活性与对照组相比显著升高(P0.05);中、高剂量组大鼠肝脏MDA含量是对照组2.5倍和3.5倍(P0.05)。低、中、高剂量组PPARα及其所调控的CYP4A1基因mRNA表达水平均被显著诱导升高。低、中、高剂量组PPARα蛋白表达均上调(P0.05)。结论 PFOA暴露可导致大鼠肝脏氧化应激,从而引起SOD和GSH-Px以及MDA的变化。同时,PFOA暴露可诱导大鼠肝脏的PPARα、CYP4A1基因表达上调,可增强脂肪酸β氧化,从而导致脂质过氧化产生,对大鼠肝脏有明显的毒性作用。
[Abstract]:Objective to study the effects of perfluorooctanoic acid (PFOAA) on oxidative stress and the expression of peroxisome proliferator activated receptor (PPAR) 伪, cytochrome P450(CYP)4A1 gene and PPAR 伪 protein in rat liver. Methods Twenty-eight male Sprague-Dawley rats were randomly divided into 4 groups, 7 rats in each group: control group (PFOA 1 mg/(kg d), middle dose group (PFOA 5 mg/(kg d) and high dose group (PFOA 25 mg/(kg d). Weigh the liver and calculate the liver coefficient. The activity of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in rat liver were determined by biochemical assay kit, and the mRNA transcription level of PPAR 伪 and CYP4A1 gene was detected by fluorescence quantitative PCR and PPAR 伪 protein expression was detected by Western blot. Results from the 5th day after gavage, the body weight of the high dose group was significantly different from that of the control group (P 0.05). Compared with the control group, the liver weight and liver coefficient of the middle and high dose groups were significantly higher than that of the control group (P 0.05). Compared with the control group, the activities of SOD and GSH-Px in the liver of the low dose group were significantly higher than those of the control group (P 0.05), while the content of MDA in the liver of the high dose group was 2.5 times and 3.5 times higher than that of the control group. In low, medium and high dose groups, the expression of PPAR 伪 and its regulated CYP4A1 gene mRNA were significantly increased. The expression of PPAR 伪 protein was up-regulated in low, medium and high dose groups. Conclusion PFOA exposure may lead to oxidative stress in the liver of rats, which may result in the changes of SOD, GSH-Px and MDA. At the same time, PFOA exposure induced the up-regulation of PPAR 伪 -CYP4A1 gene expression in rat liver, enhanced the oxidation of fatty acid 尾, and resulted in lipid peroxidation, which had obvious toxic effect on rat liver.
【作者单位】：蚌埠医学院;
【基金】：安徽省自然科学基金(No.1508085QH188,1608085QH192) 安徽省高等学校质量工程特色专业建设项目(No.2014tszy019)
【分类号】：R114

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