邻苯二甲酸二异癸酯急性染毒对小鼠肾脏的影响及其作用机制

Effects of acute exposure to diisodecyl phthalate on kidney in mice and underlying mechanism

[背景]邻苯二甲酸二异癸酯(DiDP)是一种新型增塑剂,可经多种途径进入人体。目前国内对DiDP肾毒性作用的研究不多,DiDP是否可通过氧化应激导致受试动物发生肾损伤尚不清楚。[目的]探讨不同剂量的DiDP暴露对雄性Balb/c小鼠肾脏的影响及可能机制。[方法]Balb/c小鼠随机分为空白对照组(生理盐水)、不同剂量DiDP组(0.15、1.5、15、150 mg/kg)、Vit E组(100 mg/kg)、联合处理组(150 mg/kg DiDP+100 mg/kg Vit E)共7组,每组8只。灌胃染毒14 d后,观察肾组织切片病理学变化,检测肾组织活性氧(ROS)、丙二醛(MDA)、还原型谷胱甘肽(GSH)、8-羟基脱氧鸟苷(8-OHdG)和血清尿素氮(UREA)、肌酐(CREA)水平。[结果]与空白对照组比较,150 mg/kg DiDP组小鼠肾组织ROS、MDA、8-OHd G水平及血清UREA、CREA含量升高,GSH水平降低,差异均有统计学意义(P<0.05);肾组织切片结果显示Di DP剂量越高,肾脏损伤越严重。加入Vit E干预后,与150 mg/kg DiDP组比较,联合处理组小鼠肾组织ROS、MDA、8-OHd G水平及血清UREA、CREA含量下降,GSH水平上升,差异均有统计学意义(P<0.05),同时肾组织切片结果也显示Vit E可在一定程度上降低150 mg/kg DiDP造成的肾损伤。[结论]DiDP可能通过氧化应激途径导致受试小鼠肾组织发生病理损伤。

[Background]Diisodecyl phthalate(DiDP)is a new type of plasticizer,and can enter the human body through a variety of ways.At present,there are few domestic studies on the nephrotoxicity of DiDP,and whether DiDP can cause renal injury in laboratory animals through oxidative stress is still unclear.[Objective]This experiment investigates the effects of different doses of DiDP on the kidney in male Balb/c mice,and explores the underlying mechanism.[Methods]Balb/c mice were randomly divided into control group(saline),DiDP groups(0.15,1.5,15,and 150 mg/kg),vitamin E(Vit E)group(100 mg/kg),and Vit E intervention group(150 mg/kg DiDP+100 mg/kg Vit E)(n=8 in each group).After 14 d of the designed exposure by gavage,the pathological changes of renal tissue specimens were observed;reactive oxygen species(ROS),malondialdehyde(MDA),reduced glutathione(GSH),and 8-hydroxydeoxyguanosine(8-OHdG)in renal tissues,as well as urea nitrogen(UREA)and creatinine(CREA)in serum were measured.[Results]The levels of ROS,MDA,and 8-OHdG in renal tissues and the levels of UREA and CREA in serum were significantly higher in the 150 mg/kg DiDP group than those in the control group,and the level of GSH was significantly lower(P<0.05).Moreover,the pathological results showed that higher doses of DiDP resulted in more serious renal injury.Compared with the 150 mg/kg DiDP group,the levels of ROS,MDA,and 8-OHdG in renal tissues and the levels of UREA and CREA inserum were decreased,and the GSH level was increased in the Vit E intervention group(P<0.05).Meanwhile,the pathological results showed that Vit E somewhat relieved the renal injury caused by 150 mg/kg Di DP.[Conclusion]Di DP can induce pathological damage of renal tissues in mice through oxidative stress.