4-硝基酚对大鼠肝脏的毒性及氧化损伤

研究环境内分泌干扰物4-硝基酚(4-nitrophenol,PNP)对大鼠肝脏功能的毒性作用及其对核因子相关因子-2(Nrf2)通路的影响.20只SD雄性大鼠随机分成4个组,分别为对照组、1、10和100 mg·kg-1体重PNP处理组,连续皮下注射28d,检测肝脏的结构变化、氧化损伤和Nrf2及其相关基因的表达情况.结果表明,与对照组相比,100 mg·kg-1PNP处理组大鼠的血清肝功能主要指标ALT、AST、AKP活性和TBIL含量显著性升高p＜005);100 mg·kg-1组肝脏GSH-PX、CAT和SOD活性显著性降低p＜005);大鼠肝脏中Nrf2及其下游基因NQOI和HO-1 mRNA表达水平在1mg·kg-1组显著升高(p＜0.05),10、100 mg·kg-1组有升高趋势;100 mg ·kg-1组肝脏显微和超微结构都发现有不同程度的损伤.结果提示,皮下注射1 mg·kg-1 PNP引起了大鼠肝脏氧化损伤,机体可能通过提高Nrf2及其相关基因mRNA的表达水平来抵抗PNP引起的肝脏损伤;皮下注射100 mg·kg-1 PNP改变了肝脏的正常生理功能,造成肝细胞超微结构病理损伤,引起肝脏毒性.

Effects of 4-Nitrophenol on Toxicity and Oxidative Damage in Rat Liver

This experiment was conducted to investigate the effects of PNP on the function of liver and nuclear factor erythroid 2-related factor 2(Nrf2) pathway in SD male rats. Twenty SD male rats were randomly divided into four groups, then injected subcutaneously with PNP(1, 10, 100 mg·kg^-1 body weight or vehicle) daily for 28 days. We assessed the structural changes, oxidative damage and the expression of Nrf2 and related genes in the liver. The results showed that the activities of ALT, AST, AKP and the contention of TBIL in the serum increased significantly(p<0.05) as well as the activities of GSH-PX, CAT and SOD in the liver were significantly decreased(p<0.05) in the 100 mg·kg^-1 PNP-treated group compared with the control group. In the meantime, the mRNA expression levels of Nrf2 and its downstream genes (NQO1 and HO-1) were significantly increased(p<0.05) in the 1 mg·kg^-1 as well as it tended to increase in the 10 or 100 mg·kg^-1 PNP-treated groups, there were microstructure and ultrastructure of hepatocyte damages in the 100 mg·kg^-1 PNP-treated group. In conclusion, 1 mg·kg^-1 PNP induced the lipid peroxidation and reduced oxidative damage via the Nrf2 pathway, but 100 mg·kg^-1 PNP could affect liver function, also caused pathological damage in hepatocyte architecture and liver toxicity.