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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 study the accumulation of arsenic in blood, liver, kidney and brain tissue of long-term administration of realgar in rats in order to explore the toxicity mechanism of realgar and provide a scientific basis for clinical safety medication. Methods: ① Male SD rats after fasting for 16 h were randomly divided into control group (n = 4) and realgar 0.16 g.kg-1 (n = 28). The realm group was given gavage once, and 4 rats were taken at 0.5, 1, 2, 4, 8, 16 and 36 h after administration, respectively. Whole blood, heart, liver, kidney, lung and brain , Determination of arsenic content. ② The SD rats were randomly divided into control group and realgar 0.16,0.08,0.02 g.kg-1 dose group, each group 10 (male and female each 5). Each dose group administered intragastrically once a day for a total of 3 months. 16 h after the last administration of blood, liver, kidney, brain, determination of arsenic content. Results: After a single administration of 0.16 g · kg-1 of realgar, a certain amount of arsenic was absorbed into the body and distributed in the bloodstream and in major organs such as heart, liver, lung, kidney and brain. Followed by blood> kidney> lung> liver> heart> brain. Arsenic levels in the blood are much higher than those in other organs, and this distribution may be the basis of realgar treatment of leukemia. After 3 months of repeated administration of realgar, there was some accumulation of arsenic in blood, liver, kidney and brain tissue. In the same realgar dose group, the renal arsenic accumulation fold the highest, followed by the liver. However, in the arsenic content, the arsenic content in the blood is much higher than that in other organs, and the order of the arsenic content from high to low is blood> kidney> liver> brain. Realgar long-term medication can cause mild pathological changes of liver and kidney tissue, may be related to liver and kidney accumulation of arsenic. However, there was no change in the biochemical markers related to liver and kidney toxicity, indicating that the liver and kidney are less toxic. Conclusion: Realgar soluble arsenic can be absorbed into the body and widely distributed in the major organs. Long-term medication, arsenic in the blood, kidneys, liver, brain tissue accumulation, including kidney, liver arsenic accumulation and liver and kidney toxicity. Blood is the site of the highest level of arsenic distribution and may be the basis for realgar treatment of leukemia.