本文選題：全氟辛酸 + 氧化應(yīng)激��； 參考：《衛(wèi)生研究》2017年05期

【摘要】：目的研究全氟辛酸(perfluorooctanoic acid,PFOA)致大鼠肝臟氧化應(yīng)激以及對過氧化物酶體增殖劑激活受體(PPAR)α、細(xì)胞色素P450(CYP)4A1基因以及PPARα蛋白表達(dá)的影響。方法將28只雄性SD大鼠隨機(jī)分為4組,每組7只,分別為對照組(雙蒸水)、低劑量組[PFOA 1 mg/(kg·d)]、中劑量組[PFOA 5 mg/(kg·d)]和高劑量組[PFOA 25 mg/(kg·d)],連續(xù)14 d經(jīng)口灌胃后處死,稱重肝臟并計(jì)算肝臟系數(shù)。用生化檢測試劑盒測定大鼠肝臟組織總超氧化物歧化酶(T-SOD)、谷胱甘肽過氧化物酶(GSH-Px)活性以及丙二醛(MDA)含量;熒光定量PCR檢測PPARα及CYP4A1基因的mRNA轉(zhuǎn)錄水平;Western blot檢測PPARα蛋白表達(dá)水平。結(jié)果從灌胃第5天開始,高劑量組體重與對照組差異有統(tǒng)計(jì)學(xué)意義(P0.05)。中、高劑量組肝臟重量和肝臟系數(shù)與對照組相比,均顯著升高(P0.05)。低劑量組大鼠肝臟SOD和GSH-Px活性與對照組相比顯著升高(P0.05);中、高劑量組大鼠肝臟MDA含量是對照組2.5倍和3.5倍(P0.05)。低、中、高劑量組PPARα及其所調(diào)控的CYP4A1基因mRNA表達(dá)水平均被顯著誘導(dǎo)升高。低、中、高劑量組PPARα蛋白表達(dá)均上調(diào)(P0.05)。結(jié)論 PFOA暴露可導(dǎo)致大鼠肝臟氧化應(yīng)激,從而引起SOD和GSH-Px以及MDA的變化。同時(shí),PFOA暴露可誘導(dǎo)大鼠肝臟的PPARα、CYP4A1基因表達(dá)上調(diào),可增強(qiáng)脂肪酸β氧化,從而導(dǎo)致脂質(zhì)過氧化產(chǎn)生,對大鼠肝臟有明顯的毒性作用。
[Abstract]:Objective to study the effects of perfluorooctanoic acid (PFOAA) on oxidative stress and the expression of peroxisome proliferator activated receptor (PPAR) 偽, cytochrome P450(CYP)4A1 gene and PPAR 偽 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 偽 and CYP4A1 gene was detected by fluorescence quantitative PCR and PPAR 偽 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 偽 and its regulated CYP4A1 gene mRNA were significantly increased. The expression of PPAR 偽 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 偽 -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.
【作者單位】： 蚌埠醫(yī)學(xué)院;
【基金】：安徽省自然科學(xué)基金(No.1508085QH188,1608085QH192) 安徽省高等學(xué)校質(zhì)量工程特色專業(yè)建設(shè)項(xiàng)目(No.2014tszy019)
【分類號】：R114

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