论文部分内容阅读
目的研究全氟辛烷磺酸盐(PFOS)染毒SD大鼠后,其对大鼠肝脏毒性及细胞色素P450(CYP450)亚型mRNA表达的影响。方法 40只SD雄性大鼠,随机分为5组:4个PFOS染毒组,染毒剂量分别为0.5、1.0、3.0和10.0mg/(kg.d),1个对照组。连续灌胃染毒28 d后,分析血清生化指标和观察肝脏病理变化,并检测肝脏CYP450各亚型mRNA的表达水平。结果与对照组相比,大鼠染毒PFOS 28 d后,各染毒组大鼠的体重明显降低,10.0 mg/kg染毒组大鼠的肝脏重量显著增加。各染毒组大鼠的血清谷丙转氨酶、胆汁酸等水平显著升高,三酰甘油、总胆固醇含量降低。病理检查发现,各染毒组大鼠的肝脏细胞出现浊肿、变性,甚至坏死。此外,3.0和10.0 mg/kg组大鼠肝脏的CYP1A2mRNA水平降低,而CYP17A1 mRNA水平升高。各染毒组CYP2B1 mRNA水平均升高,呈剂量效应关系。结论 PFOS的肝毒性呈剂量效应关系,并对CYP450的各个亚型有不同影响。
Objective To investigate the effects of perfluorooctane sulfonate (PFOS) on liver toxicity and cytochrome P450 (CYP450) subtype mRNA expression in SD rats. Methods Forty SD male rats were randomly divided into 5 groups: 4 PFOS treated groups, the doses were 0.5, 1.0, 3.0 and 10.0 mg / (kg · d) respectively, and 1 control group. After 28 days of continuous intragastric administration, the serum biochemical indexes and liver pathological changes were analyzed, and the expression levels of liver CYP450 subtypes were detected. Results Compared with the control group, the body weight of rats in each exposure group decreased significantly after 28 days of exposure to PFOS, and the liver weight of rats exposed to 10.0 mg / kg significantly increased. Serum levels of alanine aminotransferase, bile acid and other levels were significantly increased in all exposure groups, and triglyceride and total cholesterol levels were decreased. Pathological examination found that the liver cells of each exposure group showed turbidity, degeneration, and even necrosis. In addition, the CYP1A2 mRNA levels in the livers of the 3.0 and 10.0 mg / kg groups decreased, while the levels of CYP17A1 mRNA increased. The CYP2B1 mRNA levels in all exposure groups were increased, showing a dose-response relationship. Conclusions The toxic effects of PFOS on hepatotoxicity are dose-dependent and have different effects on each subtypes of CYP450.