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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(P<0.05)。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(P<0.05)。低剂量组大鼠肝脏SOD和GSH-Px活性与对照组相比显著升高(P<0.05);中、高剂量组大鼠肝脏MDA含量是对照组2.5倍和3.5倍(P<0.05)。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(P<0.05)。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。
Objective To investigate the effects of perfluorooctanoic acid (PFOA) on hepatic oxidative stress and the expression of peroxisome proliferator - activated receptor (PPARα), cytochrome P450 (CYP) 4A1 and PPARα in rats. Methods 28 male Sprague-Dawley rats were randomly divided into 4 groups (7 rats in each group): control group (double distilled water), low dose group (PFOA 1 mg / (kg · d)], middle dose group mg / (kg · d)] and high dose group [PFOA 25 mg / (kg · d)] for 14 consecutive days after oral gavage, weighed the liver and calculated the liver coefficient. The activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in the liver of rats were determined by biochemical detection kit. The levels of PPARα And CYP4A1 mRNA transcription level; Western blot detection of PPARα protein expression levels. Results From the fifth day after gavage, the body weight of high dose group was significantly different from that of control group (P <0.05). Compared with the control group, the liver weight and liver coefficient of middle and high dose groups were significantly increased (P <0.05). The activities of SOD and GSH-Px in the liver of low-dose group were significantly higher than those in the control group (P <0.05). The content of MDA in the liver of middle- and high-dose groups were 2.5 times and 3.5 times that of the control group (P <0.05). The mRNA levels of PPARα and CYP4A1 regulated by low, medium and high dose groups were significantly increased. PPARαprotein expression was up-regulated in low, medium and high dose groups (P <0.05). Conclusion PFOA exposure can lead to oxidative stress in rat liver, which can induce changes of SOD, GSH-Px and MDA. At the same time, PFOA exposure can induce the up-regulation of PPARα and CYP4A1 gene expression in rat liver, which can enhance the fatty acid β oxidation, leading to lipid peroxidation and obvious toxic effect on rat liver.