邻苯二甲酸二异壬酯致小鼠肝组织氧化损伤的研究

Oxidative damage of mouse liver tissue induced by diisononyl phthalate

研究邻苯二甲酸二异壬酯对小鼠肝细胞的氧化损伤.以昆明小鼠为受试动物,随机分为5组,包括1个阴性对照组、4个邻苯二甲酸二异壬酯染毒组,染毒组按0.5,5,50,500mg/kg4个剂量水平,灌胃染毒小鼠14d.以肝组织匀浆测定活性氧(ROS)、还原型谷胱甘肽(GSH)、丙二醛(MDA)和8-羟基脱氧鸟苷(8-OHd G)的含量;以肝组织细胞测定DNA-蛋白质交联(DPC)系数.随着邻苯二甲酸二异壬酯染毒剂量的升高,肝组织的ROS、MDA、8-OHd G含量和DPC系数逐渐上升,GSH含量逐渐降低,各指标呈一定的剂量-效应关系.染毒剂量为50mg/kg时,ROS、GSH、8-OHd G含量和DPC系数差异有统计学意义(P<0.05,P<0.01);染毒剂量为500mg/kg时,上述指标差异均有统计学(P<0.05,P<0.01).同时对小鼠肝组织形态进行光镜观察,结果表明,随着染毒剂量的加大,小鼠肝细胞的病理损伤越严重.较高剂量(≥50mg/kg)的邻苯二甲酸二异壬酯能造成小鼠肝组织的氧化损伤.

To investigate the oxidative damages of diisononyl phthalate on mouse liver cells, Kunming mice were randomly grouped into five groups and orally administered with drugs daily for fourteen days; the groups included one solvent control group, four diisononyl phthalate groups. The exposure doses of diisononyl phthalate groups were 0.5, 5, 50 and 500mg/kg respectively. Some liver tissues were then made into homogenates for the measurement of ROS （reactive oxygen species）, GSH （glutathione）, 8-hydroxy-2-deoxyguanosine （8-OHdG） and MDA （Malondialdehyde） contents. Meanwhile, DPC （DNA-protein Crosslink） coefficients were detected from liver cell suspension. The liver contents of ROS, MDA, 8-OHdG and DPC coefficients increased gradually in a dose-dependent manner, whereas GSH content decreased accordingly. In the exposure group with the dose of 50mg/kg, ROS, GSH, 8-OHdG contents and DPC coefficients were significantly higher than those of the control group （P〈0.05, P〈 0.01）; There were significant differences in levels of each biomarker between 500mg/kg group and control group （P〈 0.05,P〈 0.01）. Meanwhile liver tissues were sliced for physiological observation,the results showed that tissue injury were severed gradually with the increase of exposure concentration, diisononyl phthalate at certain doses （≥50mg/kg） can induce oxidative stress in mice liver.