朱砂对大鼠的肝肾毒性研究

Study on hepatoxicity and nephrotoxicity of cinnabar in rats

目的:研究朱砂的肝、肾毒性特点,提出朱砂安全用药剂量和用药时间建议,为朱砂的临床安全用药提供科学依据。方法:小鼠单次灌胃给药,测定最大耐受量。采用SD大鼠随机分为对照组和朱砂0.025,0.05,0.1,0.4,0.8 g.kg-1.d-1(相当于《中国药典》剂量高限的1/2,1,2,8,16倍)剂量组。各剂量组均每日灌胃给药1次,连续3个月,于给药后1,2,3个月和停药1个月,测定尿液定性、血常规以及血清生化指标,并观察肝、肾、心、脑等主要脏器的组织形态学变化,确定无明显不良作用水平(NOAEL)。结果:朱砂在HgS为98%、可溶性汞为21.5μg.g-1情况下,给小鼠单次灌胃给药最大耐受量达到24 g.kg-1(等于摄入可溶性汞516μg.kg-1),相当于人日用量约3 000倍,未见明显毒性反应。朱砂超过一定剂量用药达到1个月以上,肾脏和肝脏均可见与朱砂毒性有关的病理改变,其中,肾脏对朱砂更为敏感。大鼠灌胃朱砂1个月和3个月的无明显毒性剂量分别为0.1,0.05 g.kg-1.d-1(累积摄入可溶性汞64.5,96.76μg.kg-1)。按照安全系数为60计算出人服用朱砂的日允许摄入量(acceptable daily intake,ADI)约为0.000 9～0.001 7 g.kg-1.d-1,相当于60 kg人日用剂量为0.05～0.1 g。结论:反复使用朱砂时,建议在可溶性汞含量≤21μg.g-1的条件下,朱砂的用药剂量不宜超过0.05～0.1 g,用药时间不宜超过2周。

Objective:To investigate hepatoxicity and nephrotoxicity of cinnabar to provide the scientific basis for safe uses in clinic.Method:Maximally tolerated dose of cinnabar(MTD) was tested by single oral administration.Chronic toxicity of cinnabar at different dose level(0.025,0.05,0.1,0.4,0.8 g.kg-1.d-1) corresponding to 1/2,1,2,8,16 times of clinic doses of cinnabar was investigated.The rats were treated with the cinnabar through oral administration once a day for successive 90 days.Urinary qualitative test,b...