雄黄砷的蓄积性研究  

Asenic accumulation following realgar administration in rats

作　　者：李春英[1] 梁爱华[1] 王金华[1] 薛宝云[1] 李化[1] 杨滨[1] 王京宇[2] 解清[2] Odd Georg Nilsen 张伯礼[4] 

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]北京大学公共卫生学院,北京100083 [3]挪威科技大学医学院 [4]天津中医药大学,天津300193

出　　处：《中国中药杂志》2011年第14期1895-1900,共6页China Journal of Chinese Materia Medica

基　　金：国家"重大新药创制"科技重大专项(2009ZX09301);国家科技部科研院所基础研究专项基金(2002DEB20067);国家"十一五"科技支撑计划项目(2006BAI55B02-03)

摘　　要：目的:研究大鼠长期给予雄黄后砷在血液、肝脏、肾脏和脑组织中的蓄积性,以探讨雄黄的毒性机制,为临床安全用药提供科学依据。方法:①将禁食16 h后的雄性SD大鼠随机分为对照组(4只)和雄黄0.16 g.kg-1组(28只)。雄黄组灌胃给药1次,于给药后0.5,1,2,4,8,16,36 h时间点各取4只大鼠,取全血、心脏、肝脏、肾脏、肺和脑组织,测定砷含量。②将SD大鼠随机分为对照组和雄黄0.16,0.08,0.02 g.kg-1剂量组,每组10只(雌雄各5只)。各剂量组每日灌胃给药1次,共给药3个月。于末次给药后16 h取血、肝、肾、脑,测定砷含量。结果:单次给予雄黄0.16 g.kg-1后,一定量的砷能吸收进入体内,分布于血液和心、肝、肺、肾、脑等主要脏器,达峰时砷含量从高至低依次为血液>肾>肺>肝>心>脑。血液中砷水平远高于其他脏器中砷水平,这一分布特点可能为雄黄治疗白血病的基础。雄黄反复给药3个月后,血液、肝脏、肾脏和脑组织均有一定程度的砷蓄积。在相同的雄黄剂量组,肾脏的砷蓄积倍数最高,其次是肝脏。然而在砷含量方面,血液中的砷含量远高于其他脏器的砷含量,砷含量由高至低的顺序为血液>肾脏>肝脏>脑。雄黄长期用药时可造成肝、肾组织轻度病理变化,可能与肝、肾组织的砷蓄积相关。但未见血液与肝肾毒性相关的生化指标变化,说明肝脏与肾脏毒性较轻。结论:雄黄的可溶性砷可吸收入体内,广泛分布于主要脏器中。长期用药后,砷可在血液、肾脏、肝脏、脑组织蓄积,其中肾脏、肝脏砷蓄积与肝、肾毒性有关。血液是砷分布水平最高的部位,可能是雄黄治疗白血病的基础。Objective： To explore arsenic accumulation and toxicity mechanism following long-term use of realgar and provide scientific basis for safety use of realgar in clinic. Method： The realgar which was used in the study contains 90% insoluble asenic sulfide （As2S2） and 1.696 mg·kg^-1 soluble arsenic. Two separate experiments were performed： ① Twenty-eight fasting SD rats were orally given a single dose of realgar at the dose of 0.8 g·kg^-1 and the other four rats were given ultra-filtrated water served as control group. Blood, hearts, livers, kidneys, lungs and brains of four rats were taken out at 0.5, 1,2,4,8,16,36 h respectively after treatment. Asenic quantity of each organ or blood sample was measured. ②Forty SD rats were randomly divided into four groups： control group and realgar 0.02, 0.08, 0.16 g·kg^-1 groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with realgar once a day for successively 90 days, while the control group was given ultra-filtrated water. Asenic amount in blood, liver, kidney and brain of each rat was measured in fasting rats at 16 h after last dosing. Result： Asenic amount of blood, liver, kidney, heart, lung and brain increased after single dosing of realgar at dose of 0.16 g·kg^-1, with the order from high to low blood〉kidney〉lung〉liver〉heart〉brain. Asenic amount was much higher in blood than that in other organs. The feature of asenic distribution in blood following realgar administration may be the basis for its use for leukemia. Ninety-day oral treatment of realgar led to significant accumulation of asenic in blood, kidney, liver and brain. The highest asenic accumulation times was found in kidney followed by liver, which was assumed to be associated with nephrotoxicity and hepatotoxicity of realgar. The highest amount of asenic was observed in blood after 90 day＇s administration of realgar, and the amount of asenic in organs was in the order of blood〉kidney〉liver〉brain. Conclusion： Asenic can be absor

关 键 词：雄黄 矿物药 毒性 砷 蓄积 

分 类 号：R285.5[医药卫生—中药学]