孕期母体镉暴露对C57BL/6小鼠肝脏和肾脏的组织特异性氧化损伤作用

Tissue-Specific Effects of Gestational Cadmium Exposure on the Maternal Livers and Kidneys

目的:探明孕期母体镉暴露对C57BL/6小鼠肝脏和肾脏组织的氧化损伤作用。方法:将45只初始体重相近的孕鼠,于妊娠第7.5 d(E7.5)随机分为3组,饲喂不同浓度的氯化镉溶液(0、20和40 mg/L),分别于E13.5、E16.5和E19.5收集获得各组孕鼠的肝脏和肾脏组织样本,每一妊娠阶段5只孕鼠,检测各组小鼠母体肝脏和肾脏组织抗氧化酶,包括超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)活性,脂质过氧化水平(MDA含量),蛋白质羰基化(PCO含量)和DNA-蛋白质交联(DPC)水平等指标的变化情况。结果:CAT活性在肝脏和肾脏组织中随镉浓度增加逐渐升高,随时间延长逐渐降低;GPx活性在肝脏组织中随时间延长而逐渐降低,而在肾脏组织中随时间延长而逐渐升高;SOD活性在E19.5的40 mg/L镉处理组小鼠肝脏组织中显著升高;PCO含量在肝脏和肾脏组织中随镉浓度增加而逐渐升高;DPC在肝脏和肾脏组织中随镉浓度增加和时间延长而逐渐升高;而MDA含量仅在肝脏组织中随镉浓度增加而逐渐升高,随时间延长而逐渐降低。结论:孕期镉暴露对母体肝脏和肾脏产生了明显的氧化损伤,这可能与镉致胎儿生长受限的毒性效应相关;孕期镉暴露诱导的母体肝脏和肾脏的氧化损伤指标的变化具有组织特异性,这可能与镉在母体肝脏和肾脏中的积累量不同有关。

Objective： To investigate the redox homeostasis in liver and kidney of mice treated with cadmium during gestation. Methods： Fortyfive pregnant mice were randomly divided into three groups： control, experimental 1（20 mg/L of CdC12） and experimental 2（40 mg/L of CdC12）. Drinking water with or without Cd was supplied fi＇om embryonic day（E） 7.5. The dams of these three groups were sacrificed on embryonic days E13.5, E16.5 and E19.5 separately. All liver and kidney samples were collected for the assessments of the activities of antioxidant enzymes such as superoxidant dismutase（SOD）, catalase（CAT） and glutathione peroxidase（GPx） as well as the contents of malonyldialdehyde（MDA）, protein carbonyl（PCO） and DNA-protein cross links（DPC） in liver and kidney tissues. Results： The activities of CAT of the livers and kidneys increased as the Cd^2＋ concentrations increased, but decreased over time. GPx activities decreased over time in the livers, but increased over time in the kidneys. SOD activity was significantly higher in the livers of 40 mg/L group than that in the controls at E19.5. PCO contents in the livers and kidneys increased as the Cd^2＋ concentrations increased. DPC increased as the Cd^2＋ concentrations and time increased. MDA contents increased as the Cd^2＋ concentrations increased, and decreased over time. Conclusion： The gestational eadmiunl exposure causes oxidative damages on the livers and kidneys, which may be responsible for the toxicity of eadmium on fetal growth restriction under gestational eadmiunl exposure. The differenees of oxidative damages between the livers and kidneys may be due to different Cd accumulation in these tissties.