八氯代二苯并二噁英致小鼠肝脏病理损伤及Caspase-3的影响

Effects of OCDD on pathological lesions and Caspase-3 of liver in C57BL/6j male mice

目的研究八氯代二苯并二噁英(OCDD)对C57BL/6j雄性小鼠肝脏结构及Caspase-3表达的影响,探讨其对肝脏的毒性作用。方法将40只7～8周龄SPF级雄性C57BL/6j小鼠按体重随机分为4组,分别为对照组(玉米油)和低(1.25×10-6 g/ml)、中(1.25×10-5 g/ml)、高(1.25×10-4 g/ml)剂量OCDD染毒组,每组10只。采取灌胃方式进行染毒,染毒容量为8 ml/kg,1次/d,连续染毒30 d,染毒结束后观察肝脏体重比值的改变;HE染色观察肝脏的光镜结构;免疫组化法(SP法)检测肝脏组织中Caspase-3的表达。结果染毒30 d后,小鼠肝脏的结构发生了改变,染毒剂量越大结构改变越明显;与对照组比较,各染毒组小鼠肝脏体重比值增加显著(P<0.05);与对照组比较,Caspase-3蛋白在中剂量组和高剂量组表达均增高(P<0.05),其中高浓度组差异有显著统计学意义(P<0.01),且染毒剂量与Caspase-3表达存在剂量-效应关系。结论在本实验条件下,OCDD可导致小鼠肝脏损伤。

Objective To study the influence of 1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin（OCDD） on the structure and the expression of Caspase-3 of liver in C57BL/6j male mice and to investigate the mechanism of liver damage induced by OCDD.Methods Forty 7-8-week-old male mice（SPF grade） were randomly divided into four groups of 10 mice each as normal control group（maize oil）,low-dose group（1.25×10-6 g/ml,OCDD）,medium-dose group（1.25×10-5 g/ml,OCDD）and high-dose group（1.25×10-4 g/ml,OCDD）.All groups were orally gavaged with 8 ml/kg of OCDD or maize oil for 30 days.The changes of liver weight ratio were observed;the microscopic structure of the liver was observed by HE staining;the expressions of Caspase-3 in the liver tissues were detected by immunohistochemistry（SP）.Results After 30d continuous exposure,the liver structure of mice had changed,with the higher dose,the more significant changes in the structure were observed;Compared with the control group,the ratio of liver weight increased significantly in the treatment group（P0.05）;Compared with the control group,caspase-3 protein expressions were increased in medium-dose group and high-dose group（P0.05）,including the high-dose group were significantly increased（P0.05）,and there was a dose-response relationship between the exposure and Caspase-3 expression.Conclusion The mouse liver was damaged by OCDD under our experimental conditions.