DEHP对大鼠肝组织及肝细胞色素P450酶系的影响

摘要

To study the effects of di-(2-ethylhexyl) phthalate (DEHP) on hepatic tissue and cytochrome enzyme 450 in rat liver.A total of 32 male SD rats were randomly divided into 4groups (n=8per group):control group,low-dose group,medium-dose group,and high-dose group.DEHP was intragastrically administrated at the dosage of 0,300,1000 and 3000mg/kg (body weight) for 28days.The pathological changes of hepatic tissues were observed by HE staining.ELISA method was used to determine the content of CYP450,CYP2E1,CYP3A1 and PXR.Inflammatory cellular infiltration,hyperemia,vacuoles and fatty degeneration were observed in the low,middle,and high dosage groups respectively.The contents of CYP450 and CYP2E1 in the middle dosage group [(203.61±34.44)pmol/gprot,(14.57±3.03)U/gprot] and in the high dosage group [(263.73±63.78)pmol/gprot,(20.06±2.90)U/gprot] were significantly higher than that of the control group [(141.12±20.24)pmol/gprot,(10.76±2.24)U/gprot] (P＜0.01).CYP3A1 and PXR in all dosage groups increased significantly compared with the control group (P＜0.05,P＜0.01).DEHP exposure induced the levels of CYP450,CYP2E1,CYP3A1 and PXR in rat liver.%为探讨邻苯二甲酸二(2-乙基己基)酯(DEHP)染毒对雄性大鼠肝组织及肝细胞色素P450(CYP450)酶系的影响,将32只SPF级SD雄性大鼠随机分为4组:(对照组,DEHP低,中,高剂量组),每组8只,分别以0,300,1000,3000mg/kg DEHP的剂量连续灌胃染毒28d.观察肝组织病理学变化;ELISA法测定肝脏CYP450、亚型CYP2E1和CYP3A1、以及孕烷X受体(PXR)水平.结果显示,HE染色可见低,中,高剂量DEHP暴露组肝脏组织分别出现炎性细胞浸润、充血、空泡和脂肪变性等不同程度的损伤;DEHP中,高剂量组大鼠CYP450酶含量分别为(203.61±34.44),(263.73±63.78)pmol/gprot,CYP2E1酶含量分别为(14.57±3.03),(20.06±2.90)U/gprot,均显著高于对照组(141.12±20.24)pmol/gprot,(10.76±2.24)U/gprot(P＜0.01);低,中,高3个剂量组CYP3A1含量及PXR含量均同样显著高于对照组(P＜0.05或P＜0.01).DEHP暴露对大鼠肝组织有损伤作用,对肝脏CYP450、CYP2E1、CYP3A1以及上游调节因子PXR具有诱导效应.