朱砂灌胃给药后汞在孕大鼠脏器内的分布和排泄途径研究

Study on Distribution in Organs and Excretion Pathway of Mercury in Pregnant Rats after Administration of Cinnabar

目的:探讨朱砂口服后汞在孕大鼠体内的分布和排泄途径。方法:结合生殖毒性Ⅱ段试验,雌性SD大鼠交配后随机分成朱砂悬液高(1 000 mg/kg)、中(300 mg/kg)、低(100 mg/kg)剂量组和阴性对照组(0.5%CMC-Na)4组,妊娠第6天至第15天每天1次,连续灌胃10 d,于妊娠第20天处死。取孕大鼠各主要脏器(心、肝、脾、肺、肾、脑、子宫)和全血、胎盘、胎仔、尿液,每组10只,用电感耦合等离子体质谱法(ICP-MS);取不同时间的粪便,用电感耦合等离子体发射光谱法(ICP-AES),分别测定汞含量,分析汞在各脏器的分布情况以及排泄途径。结果:在测定的各脏器中,心、肝、肾和子宫组织内汞含量均高于阴性对照组,并随剂量的增加而增加;脑、肺、胎盘和胎仔组织内各剂量组的汞含量与阴性对照组比较,差异无统计学意义。给药第2天粪便中就出现大量汞,日排泄量折合成HgS约占摄入量的38.2%～50.4%;而给药第10天日排泄量上升到72.2%～86.6%;停药第4天粪便中HgS排泄量急剧下降。尿液中排泄的汞极其微量,并有剂量依赖性,停药第4天排泄量仍在较高水平。结论:①汞在不同脏器内蓄积与给药剂量有关,其中以肾、肺、子宫、肝内汞含量较高;②血脑屏障和胎盘屏障在阻止汞进入脑内和胎儿内上可能具有一定作用,但应谨慎评价;③口服朱砂主要经肠道排泄,而组织内蓄积汞的排泄可能经肾脏排泄。

Objective： To study the distribution and excretion pathway of mercury in pregnant rats after administration of cinnabar.Methods： Compared with the reproductive toxicity test,the female SD rats after mating were randomly divided into high（1 000 mg/kg）,medium（300 mg/kg）,and low-dose（100 mg/kg） cinnabar groups,and negative control group（0.5% CMC-Na）,with ten rats in each group.The rats in different dose cinnabar groups were administered intragastrically with cinnabar from the sixth day to the fifteenth day after pregnancy,and all the rats were sacrificed on the twentieth day of pregnancy.The main organs（including heart,liver,spleen,lung,kidney,brain and uterus）,blood,placentae,fetuses and urine of the pregnant rats were obtained to detect the mercury concentration by inductively coupled plasma mass spectrometry（ICP-MS）;the feces were taken at different time points to determine the mercury concentration by inductively coupled plasma optical emission spectrometer（ICP-OES）;the distribution in different organs and the excretion pathway of mercury were analyzed.Results： The mercury concentrations of the heart,liver,kidney and uterus of the rats in different dose cinnabar groups were higher than those of the rats in negative control group,and the concentration increased with the enhanced dose;there was no statistical difference on the mercury concentrations of the brain,placentae and fetuses between different dose cinnabar groups and negative control group.There were large amount of mercury in the feces on the second day after administration,and the mercury excretion accounted for 38.2%~50.4% of HgS intake;while the mercury excretion accounted for 72.2%~86.6% on the tenth day after administration;The amount of HgS discharged in the feces decreased rapidly on the fourth day after drug discontinuation.Only extreme trace of mercury excreted from urine with dose-dependent pattern,and the mercury excretion maintained the high levels on the fourth day after drug discontinuation.Conclusion： ①The mercury accumulation in different organs after administration of cinnabar is related with the dosage,and the concentrations in kidney,lung,uterus and liver are higher.②The blood-brain barrier and placenta barrier may play a certain role in preventing mercury from entering the brain and fetus,but the evaluation should be made with caution.③The main excretion pathway after administration of cinnabar is intestinal tract,while the mercury accumulated in tissues may excrete through kidney.