Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, China.
Department of Pathology, School of Basic Medical, Shanxi Medical University, Taiyuan, China.
Toxicol Appl Pharmacol. 2019 Oct 15;381:114730. doi: 10.1016/j.taap.2019.114730. Epub 2019 Aug 22.
Vinyl chloride (VC) is a common industrial organochlorine, shown to cause hepatic angiosarcoma and hepatic steatosis. However, the role of endoplasmic reticulum stress (ERS) and oxidative stress (OS) in hepatic steatosis after subchronic exposure to VC in mice, is unclear. Based on body weight, forty healthy SPF male C57BL/6 J mice were randomly divided into a control group and three VC exposure groups (57.3, 286.7, and 1433.6 ppm) (n = 10 each). VC was administered by static inhalation in a 50 L sealed plexiglass inhalation chamber for 2 h per day, five days per week for 16 weeks. Serum and liver tissues were analyzed for liver enzymes and lipids. Hepatic cytochrome P450 2E1 (CYP2E1) and OS related indicators malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were measured. The mRNA expressions of ERS downstream genes, including glycoregulatory protein-78 (GRP-78), sterol regulatory element binding protein-1 (SREBP-1), Acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) were detected by real-time PCR (RT-PCR) and their protein levels examined by western blotting. The CYP2E1 levels increased after VC administration in a dose-dependent manner. MDA levels increased (P < .05) and SOD and GSH levels decreased (P < .05) in the liver of each group with the increase in the dose of VC. ERS and expressions of downstream genes (GRP-78, SREBP-1, ACC, and FAS) were enhanced after VC administration. These results suggested that OS and ERS could be induced by VC, which may lead to an increase in fatty acid synthesis in the liver, further aggravating hepatic steatosis.
氯乙烯（VC）是一种常见的有机氯工业化合物，已被证明可导致肝血管肉瘤和肝脂肪变性。然而，在亚慢性 VC 暴露后，内质网应激（ERS）和氧化应激（OS）在小鼠肝脂肪变性中的作用尚不清楚。基于体重，将 40 只健康 SPF 雄性 C57BL/6J 小鼠随机分为对照组和三个 VC 暴露组（57.3、286.7 和 1433.6ppm）（每组 10 只）。VC 通过静态吸入法在 50L 密封有机玻璃吸入室中进行，每天 2 小时，每周 5 天，共 16 周。分析血清和肝脏组织中的肝酶和脂质。测量肝细胞色素 P450 2E1（CYP2E1）和 OS 相关指标丙二醛（MDA）、谷胱甘肽（GSH）和超氧化物歧化酶（SOD）。通过实时 PCR（RT-PCR）检测 ERS 下游基因包括糖调节蛋白-78（GRP-78）、固醇调节元件结合蛋白-1（SREBP-1）、乙酰辅酶 A 羧化酶（ACC）和脂肪酸合酶（FAS）的 mRNA 表达，并通过 Western 印迹法检测其蛋白水平。VC 给药后 CYP2E1 水平呈剂量依赖性增加。随着 VC 剂量的增加，各组肝脏中 MDA 水平升高（P<.05），SOD 和 GSH 水平降低（P<.05）。ERS 和下游基因（GRP-78、SREBP-1、ACC 和 FAS）的表达增强。这些结果表明，OS 和 ERS 可能被 VC 诱导，导致肝脏中脂肪酸合成增加，进一步加重肝脂肪变性。
