生熟大黄总提取物灌胃给药后游离蒽醌在SD大鼠组织中的分布差异研究  

Tissue distribution of free anthraquinones in SD rats after orally administered extracts from raw and prepared rhubarbs

作　　者：方芳[1,2] 王伽伯[1] 赵艳玲[1] 金城[1] 孔维军[1,2] 赵海平[3] 王红娟[1] 肖小河[1] 

机构地区：[1]解放军中药研究所,解放军第三〇二医院,北京100039 [2]成都中医药大学,四川成都610075 [3]江西中医学院,江西南昌330004

出　　处：《药学学报》2011年第3期350-354,共5页Acta Pharmaceutica Sinica

基　　金：国家“重大新药创制”科技重大专项资助项目(2009ZX09502-022);国家自然科学基金资助项目(30973947);国家公益性行业科研专项基金资助项目(200807020)

摘　　要：大黄应用范围广、疗效确切,然而近年来国内外实验报道大黄中蒽醌成分具有肝、肾细胞毒性。本文对比研究了生熟大黄总提取物灌胃给药后游离蒽醌在正常SD大鼠组织中的分布。肝、脾和肾组织中游离蒽醌类成分含量采用UPLC-MS/MS法测定。生熟大黄总提物(相当于生药量14.69 g.kg-1)灌胃给药,连续12周。结果表明,游离蒽醌在生大黄组大鼠组织中的分布浓度高于熟大黄组;大黄游离蒽醌在同一组织中的分布浓度顺序大致为大黄酸>大黄素>芦荟大黄素;大黄酸在肝、脾和肾组织中的分布浓度明显高于芦荟大黄素和大黄素,且大黄酸在生大黄组的组织分布浓度明显高于熟大黄组;停药恢复4周后,大黄游离蒽醌在组织中检测不到。结果提示生大黄的组织毒性可能高于熟大黄;大黄酸可能是大黄主要的毒性物质之一;大黄游离蒽醌在组织中可能无蓄积毒性。炮制过程不仅影响了有效成分的含量还可能影响其成分的组成,通过影响吸收和作用过程中成分之间的相互作用,致使生大黄组动物组织中游离蒽醌的分布浓度高于熟大黄组,这与传统中医药理论炮制减毒的思想认识基本一致。Rhubarb anthraquinone derivatives（AQs） have been documented to have both therapeutic and toxic effect on liver and kidney,leading to a complex puzzle to assess their benefits and risks.In this study,the tissue distributions of AQs in SD rats after orally administrated extracts of raw and prepared rhubarb were examined whether they undergo different uptake.The total rhubarb extract（14.49 g·kg-1 of body weight per day od,counted on the quantity of crude material） was administrated orally for 12 weeks.The concentrations of the AQs in different tissues were quantified by liquid chromatography-tandem mass spectrometry（LC-MS/MS）.The five major AQs,aloe-emodin,rhein,emodin,chrysophynol and physcion,could all be detected in the liver,kidney and spleen,while only rhein,aloe-emodin and emodin reached the quantitative limit.The tissue concentrations of AQs in raw rhubarb group were higher than that in steamed rhubarb group with rhein emodin aloe-emodin in the same tissue.On the whole,the tissue distribution of rhein was higher than that of emodin and aloe-emodin in liver,spleen and kidney.AQs could not be detected in those tissues after drug withdraw for 4 weeks,which suggested scarcely any accumulative toxicity of rhubarb.The result indicated that raw rhubarb had more tissue toxicity than steamed rhubarb and rhein may be one of the major poisonous ingredients.The results were concordant with the traditional Chinese medicine theory of toxicity-attenuating effect of processing.

关 键 词：大黄 蒽醌衍生物 组织分布 UPLC-MS/MS 炮制减毒 

分 类 号：R969.1[医药卫生—药理学]