雄黄灌胃给药后砷在孕大鼠脏器内的分布及排泄途径研究

目的研究口服雄黄后砷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高、中、低（550、250、125 mg/kg）剂量组和阴性对照组（0.5%羧甲基纤维素钠）4组,妊娠第6-15日每日1次用雄黄悬浊液连续灌胃10 d,于妊娠第20日处死。每组10只,取孕大鼠各主要脏器（心、肝、脾、肺、肾、脑、子宫）和全血、胎盘、胎仔及不同给药时间点的尿液和粪便,运用电感耦合等离子体质谱法（ICP-MS）、电感耦合等离子体发射光谱法（ICP-OES）分别测定砷含量,分析砷在各脏器的分布情况以及排泄途径。结果各脏器中砷含量均显著高于阴性对照组,全血砷含量最高,并随剂量的增加而增加;与其他脏器比较,脑和胎仔组织内各剂量组的砷含量最低。给药第2日粪便中即出现大量砷,日排泄量折合成雄黄约占摄入量的69.5%～80.2%;而给药第10日排泄量上升到85.2%～96.2%;停药第4日粪便中雄黄排泄量急剧下降。尿液中排泄的砷微量,并有剂量依赖性,停药第4日排泄量仍在较高水平。结论砷在不同脏器内蓄积与给药剂量有关,其中以全血、脾、胎盘、肺内砷含量较高;口服雄黄主要经肠道排泄,而组织内蓄积的砷可能经肾脏排泄。

Distribution of Arsenic in Organs and Discharge Routes of Pregnant Rats after Administration of Realgar

Objective To study the in vivo distribution and excretion pathway of arsenic in pregnant rats after i.g.administration of realgar.Methods Integrated with reproductive toxicity on embryo-fetal development test,female SD rats were divided into high-,medion-,low-dose(550,250,125 mg/kg) realgar group and negative control group(0.5% CMC-NA).Realgar suspension liquid was given to pregnant rats during 6-15th day pregnancy.Rats were killed at 20th day,some major organs(heart,liver,spleen,lung,kidney,brain,and uterus) and the blood,placentae,fetuses were taken from pregnant rats when anatomical examination to detect the arsenic concentration by ICP-MS,and feces taken from different time intervals by ICP-OES,analyzing the arsenic distribution in main organs and excretion pathway.Results The arsenic concentrations of heart,liver,kidneys and uterus from the pregnant rats given realgar were significantly higher than that from negative control,the arsenic concentrations of whole blood being the highest,and rose with the doses increased.The arsenic concentrations of the brain and fetuses were the lowest compared with the other organs.The feces discharged large amount of arsenic the day after administration,accounting for 69.5%-80.2% of realgar intake,while the discharge increased to 85.2%-96.2% in the 10th day of administration.The amount of realgar discharged in the feces decreased rapidly in the 4th day after stopping administration.Urine excreted extreme trace of arsenic with dose-dependent relationship,maintaining high levels of excretion in the 4th day after withdrawal.Conclusion Arsenic accumulation in organs after administration of realgar is related with the dose given,the concentrations being higher in blood,spleen,placentas and lung.The main excretion pathway after administration is intestinal tract,while arsenic accumulated in tissues may excrete through kidney.