妊娠小鼠子宫对2,3,7,8-四氯苯二噁英毒性的敏感性研究

对妊娠早期小鼠用不同剂量的TCDD进行处理，妊娠第9天采集血清、肝、肾、脑、脂肪、子宫和胎儿等样品，利用酵母报道基因系统进行组织中TCDD含量检测，结果发现脂肪中TCDD含量最高，其次是肝脏、子宫和胎儿．由于TCDD的毒性需通过体内包括细胞色素P4501A2在内的代谢酶的活化，采用免疫组化的方法对TCDD诱导的该酶的表达水平进行了检测，发现肝脏和子宫的阳性反应最强，并且所需剂量很低，肾脏和脂肪组织在较高剂量出现阳性反应，而脑组织则仅在更大剂量时出现微弱的阳性信号．此现象说明子宫和肝脏一样，可以通过芳香烃类受体诱导细胞色素P4501A2酶的产生，活化TCDD，引起对细胞的毒性并产生对胚胎的毒性．在低剂量时观察到的强烈的生殖毒性应该和TCDD在子宫的蓄积和子宫内敏感的细胞色素P4501A诱导能力有关．

Study on the toxical sensitivity of uterus of pregnant mouse by using TCDD

The distribution of TCDD in tissue is key important for investigation of TCDD caused early embryo loss of pregnant mouse. By using a newly established yeast gene report system, TCDD content in liver, kidney, brain, fat, uterus and embryo of pregnant mouse were analyzed after had been taken different dosage of TCDD orally. The results showed that fat tissue accumulated highest amount of this toxin; liver, uterus and embryo also accumulated high concentration of TCDD from high to low. Since TCDD needed to be activated by its induced enzyme including cytochrome P450 1A2, the levels of enzyme were tested using immunohistochemical assay in different toxicity treatment. The highest signal was observed in liver and uterus, even in low dosage treatment, implying that uterus was an important sensitive target tissue of TCDD toxin. Positive signals were observed in kidney and fat at high dosage group, and only few cells in brain tissue could show the weak signals. These results implied that uterus was another TCDD metabolizing organ similar to liver, in which TCDD was converted into activating forms by cytochrome P450 1A2 enzyme. The high accumulation of TCDD in uterus, as well as high sensitivity for inducing cytochrome P450 1A2 enzyme mediated by AhR in uterus could explain the reason of early embryo loss in pregnant mouse at low dosage treatment.