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目的对慢性低剂量暴露于2,3,7,8-四氯二苯并二噁英(TCDD)的雌性SD大鼠血清蛋白改变进行研究,对TCDD毒性效应作进一步阐述。方法雌性SD大鼠随机分为3个染毒组和1个对照组[(n=8只/组,0 ng/(kg.d)、20 ng/(kg.d)、50 ng/(kg.d)、125 ng/(kg.d)],灌胃染毒29周,采用双向凝胶电泳和基质辅助激光解吸飞行时间串联质谱技术对大鼠血清进行蛋白组学研究,寻找差异蛋白点,并对其肝脏进行组织病理学检测。结果上调的蛋白包括补体C4,载脂蛋白A-Ⅳ前体和低分子量的激肽原前体;触珠蛋白和补体C3仅在染毒组大鼠凝胶中被识别,而对照组未见;而α-抑制因子Ⅲ前体只在对照组的胶上被识别。肝脏组织病理学检测显示染毒组大鼠肝脏出现肝细胞的脂肪变性、空泡形成、肝细胞坏死等改变,并且随染毒剂量的增加严重程度增加。结论慢性低剂量染毒使得血清蛋白谱发生改变,所改变的蛋白质与TCDD的免疫毒性、肝毒性、氧化应激等效应有关。血清差异蛋白可为TCDD毒作用分子标志物的筛选提供依据。
Objective To study the changes of serum protein in female SD rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in chronic low-dose. The toxic effects of TCDD were further elucidated. Methods Female Sprague-Dawley rats were randomly divided into 3 exposure groups and 1 control group (n = 8 / group, 0 ng / (kg · d), 20 ng / (kg · d), 50 ng / (kg .d), 125 ng / (kg · d)] for 24 weeks. The rats were subjected to proteomics study by two-dimensional gel electrophoresis and matrix-assisted laser desorption-time of flight tandem mass spectrometry , And histopathological examination of the liver was performed.Results Up-regulated proteins included complement C4, apolipoprotein A-Ⅳ precursor and low-molecular-weight kininogen precursor; Gel was identified, while the control group did not see; and α-inhibitor III precursor was only identified in the control group on the gel.Histopathological examination showed that the liver of rats exposed to hepatic steatosis, empty Formation of hepatocytes, necrosis of hepatocytes, etc., and increased with the increase of exposure dose.CONCLUSIONS Chronic low doses lead to changes of serum protein profile, changes of immunotoxicity, hepatotoxicity, oxidative stress, etc. of proteins and TCDD Effect.The serum differential proteins provide the basis for the screening of TCDD toxic molecular markers.