PFOS致大鼠肝毒性及其作用机制研究

The Mechanism of PFOS Inducing Liver Toxicity in Rats

通过全氟辛烷磺酸(perfluomoctane sultanate,PFOS)大鼠灌胃染毒实验评价PFOS对肝功能的影响,探讨PFOS肝毒性反应的潜在机制与可能途径。将Sprague Dawley (SD)雄性大鼠随机分为3组,分别以0 mg·kg^(-1)、5 mg·kg^(-1)和10 mg·kg^(-1)PFOS灌胃染毒28 d。以HE和油红染色法观察大鼠肝脏形态改变。ELISA法测定各组谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate transaminase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)含量变化。化学比色法测定肝匀浆脂代谢水平和氧化产物含量。RT-PCR法检测肝脏内氧化应激以及脂代谢相关基因表达水平。结果表明,PFOS暴露大鼠体重显著降低而肝脏系数显著增加(P<0.05),与对照组相比PFOS组血清肝功能酶均出现随PFOS浓度增加而升高(P<0.05)。同时大鼠肝脏谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-px)和丙二醛(malondialdehyde,MDA)水平在高剂量组显著升高(P<0.05),超氧化物歧化酶(superoxide dismutase,SOD)含量先显著升高(P<0.05)后显著降低(P<0.05)。且肝脏中脂代谢水平也随PFOS浓度的增加而出现显著改变(P<0.05)。PFOS组基因表达均较对照组显著上升(P<0.05)。以上结果说明PFOS具有明显的肝毒性作用,可影响肝脂代谢水平,这可能与PFOS引起的氧化应激所导致的损伤有关。

In order to reveal the toxic effect of perfluorooctane sulphonic acid( PFOS) on SD male rats,the potential mechanisms and possible pathways of PFOS hepatotoxicity were investigated in this study. 30 male SD rats were randomly divided into three groups and 0,5,10 mg·kg-1 PFOS were gavaged continuously for 28 days. Morphological changes of the rats liver tissue were examined by HE and Oil red staining. The contents of alanine aminotransferase( ALT),aspartate transaminase( AST),alkaline phosphatase( ALP) in serum were determined by ELISA.The content of triglyceride( TG) and total cholesterol( TC) in the liver was measured by chemical colorimetry. Activity of superoxide dismutase( SOD) was determined by Xanthine oxidase kits and glutathione peroxidase( GSHPx) was determined by DTNB directly. Malondialdehyde( MDA) in SD male rats was measured by Glucosinolates barbituric kits. At the same time,real time fluorescence quantitative PCR was used to detect the levels of gene( Nrf2,NQO1,HO-1,CD36 and SREBP1 c) expression related to oxidative stress and lipid metabolism. The results demonstrated that body weight of rats exposed to 10 mg·kg-1 PFOS showed significant deterioration and the liver coefficient of rats exposed to 5 mg·kg-1 and 10 mg·kg-1 were significantly increased compared with the control in male rats( P<0.05). Compared with the control,the levels of ALT,ALP and AST increased significantly( P <0.05).Furthermore,the GSH-Px activity and MDA content in 10 mg·kg-1 PFOS exposure group and MDA content in 5 mg·kg-1 PFOS exposure group were significantly increased compared with the control in male rats( P < 0.05). While SOD activity was increased significantly in 5 mg·kg-1 PFOS group( P < 0.05) and was reduced significantly in10 mg·kg-1 PFOS group( P < 0.05). In addition,the level of TG in liver was increased while TC was reduced in 5 mg·kg-1 PFOS group and increased significantly in 10 mg·kg-1 PFOS group( P < 0.05). Several genes related to oxidative stress and lipid metabolism such as Nrf2,HO-1,CD36 and SREBP1 c were significantly upregulated in PFOS exposure groups. In conclusion,these results suggest that PFOS has obvious liver toxicity,which may affect the level of liver lipid metabolism. It may be related to the damage caused by PFOS-induced oxidative stress.