孕期和哺乳期暴露壬基酚对仔鼠肝脏细胞色素P450 2E1 mRNA及蛋白表达的影响

目的 探讨孕期和哺乳期暴露壬基酚(NP)对仔鼠肝脏细胞色素P450 2E1 (CYP2E1) mRNA和蛋白表达的影响.方法 将孕鼠分为低、中、高剂量染毒组(分别给予50、100、200 mg·kg-1·d-1 NP染毒)和对照组,孕鼠受孕第6天到仔鼠出生21 d灌胃染毒NP.仔鼠出生90 d后处死,检测血清肝功能指标及血脂水平,观察肝脏病理学变化,测定肝组织谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)水平,检测CYP2E1 mRNA和蛋白表达水平.结果 与时照组比较,各染毒组仔鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平及AST/ALT比值均升高(P＜0.05),且随染毒剂量的增加呈上升趋势;血清三酰甘油(TG)、总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)水平均较对照组升高(P＜0.05).对照组仔鼠肝组织结构正常,低剂量染毒组仔鼠肝脏肝窦轻度扩张,中剂量染毒组仔鼠肝脏有轻度炎性细胞灶性浸润,高剂量染毒组仔鼠肝脏有大量脂滴存在.各染毒组仔鼠肝组织SOD、GSH-PX活性明显低于对照组(P＜0.05),MDA水平明显高于对照组(P＜0.05).中、高剂量染毒组与对照组比较CYP2E1 mRNA和蛋白表达水平均升高(P＜0.05).结论 孕期和哺乳期暴露NP,可致仔鼠肝脏脂质代谢紊乱及炎性损伤,可能与肝脏CYP2E1表达上调有关.

Effects of nonyphenol exposure during pregnant and lactation period on expressions of CYP2E1 mRNA and protein of hepatic tissues in offspring rats

Objective To investigate the effects of nonyphenol (NP)exposure during pregnant and lactation period on expression of cytochrome P450 2E1 (CYP2E1) mRNA and protein of hepatic tissues in offspring rats.Methods Pregnant rats were assigned to four groups:the exposure groups received gavage with NP at dose levels of 50 mg · kg-1 · d-1 (low dose group),100 mg · kg-1 · d-1 (medium dose group),200 mg · kg-1 · d-1 (high dose group) and the control group was treated with corn oil alone,NP exposure time was limited from gestational day 6 to postnatal day 21.The newborn rats were sacrificed at 90 days after birth,followed by blood collection and serum separation.Then,serum biochemical indicators of liver function and lipid levels were detected.Glutathione peroxidase (GSH-PX),superoxide dismutase (SOD) activities,malondialdehyde (MDA) level and CYP2E1 mRNA and protein levels were determined in hepatic tissues.Pathologic changes in hepatic tissues were observed with HE staining.Results Compared with the control group,the aspartate aminotransferase (ALT),alanine aminotransferase (AST) levels and AST/ALT ratio of offspring rats in exposure groups were increased in a dose-dependent manner (P＜0.05),as well as serum TG,TC and LDL-C levels were increased (P＜0.05).The liver tissue structure of the control group was normal.The hepatic sinus of the medium dose group was showed mild expansion and inflammatory cellular infiltration.Otherwise,the liver of high dose group had a large amount of lipid droplets.Compared with the control group,SOD and GSH-PX activities were obviously decreased,while MDA level was significantly decreased in each exposure group (P＜0.05).CYP2E1 mRNA and protein expression levels of medium and high dose groups were higher than those in the control group (P＜0.05).Conclusion Exposure to NP during gestation and lactation period can induce lipid metabolism disorders and inflammatory lesions in hepatic tissues of offspring rats,and it maybe associated With up-regulation of CYP2E1 expression.