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季戊四醇脂肪酸酯对斑马鱼胚胎发育及幼鱼肝脏抗氧化酶活力的影响。

Lipid accumulation responses in the liver of Rana nigromaculata induced by perfluorooctanoic acid (PFOA).

机构信息

College of Life and Environmental Sciences, Hangzhou Normal University, Xuelin Road 16#, Xiasha Gaojiao Dongqu, Hangzhou, Zhejiang Province 310036, China; Guangzhou Key Laboratory of Environmental Exposure and Health, School of Environment, Jinan University, Guangzhou 510632, China; Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, Hangzhou Normal University, Hangzhou, Zhejiang Province 310036, China.

College of Life and Environmental Sciences, Hangzhou Normal University, Xuelin Road 16#, Xiasha Gaojiao Dongqu, Hangzhou, Zhejiang Province 310036, China.

出版信息

Ecotoxicol Environ Saf. 2019 Jan 15;167:29-35. doi: 10.1016/j.ecoenv.2018.09.120. Epub 2018 Oct 4.

Abstract

Perfluorooctanoic acid (PFOA) is a perfluorinated compound that is widely distributed, is persistent in the environment, and has a low-level chronic exposure effect on human health. The aim of this study was to investigate the peroxisome proliferator activated receptors γ (PPARγ) and the sterol regulatory element-binding protein 2 (SREBP2) signaling pathways in regulating the lipid damage response to PFOA in the livers of amphibians. Male and female frogs (Rana nigromaculata) were exposed to 0, 0.01, 0.1, 0.5 and 1 mg/L PFOA. After treatment, we evaluated the pathological changes in the liver by Oil Red O, staining and examined the total cholesterol (T-CHO) and triglyceride (TG) contents. The mRNA expression levels of PPARγ, Fatty acid synthase (FAS), Acetyl-CoA carboxylase (ACC), Glycerol-3-phosphate acyltransferase (GPAT), SREBP2 and 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The administration of PFOA caused marked lipid accumulation damage in the amphibian livers. The T-CHO contents were elevated significantly after PFOA treatment; these results show a dose-dependent manner in both sexes. The TG content showed a significant increase in male livers, while it was elevated significantly in female livers. The RT-PCR results showed that the mRNA expression levels of PPARγ, ACC, FAS, GPAT, SREBP2 and HMG-CoA were significantly dose-dependently increased in the PFOA-treated groups compared with those of the control group. Our results demonstrated that PFOA-induced lipid accumulation also affected the expression levels of genes FAS, ACC, GPAT and HMG-CoA in the PPARγ and SREBP2 signaling pathways in the liver. These finding will provide a scientific theoretical basis for the protection of Rana nigromaculata against PFOA effects.

摘要

全氟辛酸(PFOA)是一种全氟化合物,广泛分布,在环境中持久存在,对人类健康具有低水平的慢性暴露效应。本研究旨在探讨过氧化物酶体增殖物激活受体γ(PPARγ)和固醇调节元件结合蛋白 2(SREBP2)信号通路在调节两栖动物肝脏中 PFOA 诱导的脂质损伤反应中的作用。雄性和雌性青蛙(Rana nigromaculata)暴露于 0、0.01、0.1、0.5 和 1mg/L 的 PFOA 中。处理后,我们通过油红 O 染色评估肝脏的病理变化,并检测总胆固醇(T-CHO)和甘油三酯(TG)含量。通过定量实时聚合酶链反应(qRT-PCR)测量 PPARγ、脂肪酸合酶(FAS)、乙酰辅酶 A 羧化酶(ACC)、甘油-3-磷酸酰基转移酶(GPAT)、SREBP2 和 3-羟-3-甲基戊二酰辅酶 A(HMG-CoA)的 mRNA 表达水平。PFOA 处理导致两栖动物肝脏明显的脂质积累损伤。T-CHO 含量在 PFOA 处理后显著升高;这些结果在两性中均表现出剂量依赖性。TG 含量在雄性肝脏中显著增加,而在雌性肝脏中显著增加。RT-PCR 结果表明,与对照组相比,PFOA 处理组中 PPARγ、ACC、FAS、GPAT、SREBP2 和 HMG-CoA 的 mRNA 表达水平均显著剂量依赖性增加。我们的结果表明,PFOA 诱导的脂质积累也影响了 PPARγ 和 SREBP2 信号通路中 FAS、ACC、GPAT 和 HMG-CoA 基因的表达水平。这些发现将为保护黑斑蛙免受 PFOA 影响提供科学理论依据。

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