PBDE-209致小鼠肝脏病理学改变及其氧化应激机制研究

目的 通过对小鼠进行十溴联苯醚(decabrominated diphenyl ether,PBDE-209)染毒,研究该物质对小鼠肝脏的毒性作用及其可能的氧化应激机制.方法 将24只小鼠随机分3组,即生理盐水组、PBDE-209低剂量组和高剂量组,每组8只,将小鼠按10ml/kg体重剂量经口灌胃染毒连续6周,观察各组小鼠肝脏组织形态学和超微结构改变,并测定小鼠各项生化指标.结果 染毒组小鼠血清谷丙转氨酶和谷草转氨酶水平均升高,与生理盐水组比较,差异有统计学意义.高、低剂量组小鼠肝脏组织丙二醛含量均高于生理盐水组,差异有统计学意义；高剂量组小鼠肝脏谷胱甘肽含量低于生理盐水组和低剂量染毒组,差异有统计学意义；高、低剂量组总超氧化物歧化酶活性低于生理盐水组,差异有统计学意义.光镜下观察染毒组小鼠肝脏出现肝细胞浊肿,胞浆内有细小脂质空泡,肝索排列发生改变,部分肝细胞模糊,空泡化显著；电镜下观察染毒组小鼠肝脏出现染色质浓缩聚合,线粒体膨胀,内质网增大.结论 PBDE-209可以引起肝脏组织脂质过氧化指标和组织形态学以及超微结构的改变.

Study on pathological changes in mice liver induced by PBDE-209 and the mechanism of oxidative stress

Objective To explore the hepatotoxicity and the possible mechanisms of oxidative stress through the mice exposed to decabrominated diphenyl ether（PBDE-209）.Methods Twenty four mice were randomizedly divided into three groups with eight mice in each： blank control,low and high dose group.All the groups were exposed by oral gavage.The mice were sacrificed after 6 weeks PBDE-209 treatment.Morphological and ultrastructural changes of liver were observed.The levels of alanine aminotransferase（ALT）,aspartate aminotransferase（AST） in serum and malonyldialdehyde（MDA）,total superoxide dismutase（T-SOD） and glutathione（GSH） in liver were analyzed.Results The serum ALT and AST levels of the mice exposed to PBDE-209 were significantly increased compared with the control group,and the difference was statistically significant（P0.05）.The levels of MDA in liver in both high and low dose group were higher than that in control group.Liver GSH level in high dose group were decreased compared with the levels in control and low dose group and the difference was statistically significant（P0.05）.The activity of T-SOD in high and low dose group were lower than that in control group.In light microscopy,cloudy swelling of liver cells was found in the liver of mice exposed to PBDE-209,small lipid vacuoles were also found in the cytoplasm,hepatic cord arrangement was changed,part of the liver cells were vague,vacuolization was significant.The ultrastructural changes included condensation and margination of chromatin,swollen mitochondria,and enlargement of endoplasmic reticulum.Conclusions PBDE-209 exposure can cause the change of liver＇s morphology and ultrastructure.Excessive PBDE-209 may induce oxidative stress in the liver of mice.