炮制对大黄化学成分和肝肾毒性的影响及其典型相关分析十，马永聊凸，蛀琦,Im,1,2灿平摘要：木文采用典型相关分析方法探讨人黄炮制减毒和化学成分改变间的相关性。通过亚急性毒性试验比较大黄不同炮制品肝肾毒性的差异，恿醍、糅质类成分含量采用UV-Vis显色法和高效液相色谱法测定。莓性考察结果表明，生大黄故大给药:®(76gkg*)给小鼠连续灌胃14天，可见肝肾损伤作用，而不同炮制品的毒性相对较小，衣明炮制具有减毒作用。化学成分弓肝肾功能生化指标的典型相关分析结果表明，大黄中所含大类成分与肝肾毒性的相关性顺序为总结合恿:醱>总糅质>总游离蔥Hi;游离态蔥醍肝肾毒性顺序为芦荟大黄素>大黄素甲储>大黄酸>大黄素>大黄酚；结合态恿醍肝肾毒性顺序为结合芦荟大黄素>结合大黄索甲储>结合人黄酚>结合人黄素>结合人黄酸。提示炮制可降低人黄肝肾毒性，其机制与结合葱服和糅质类成分的下降冇关，其中游离和结合态的芦荟人黄素及人黄素甲讎与毒性和关性最强。肝肾生化功能指标中，血淸谷丙转氨酶(ALT)和肌苛(CREA)反映肝肾毒性较敏感，提示可作为临床安全性监测指标。关键词：炮制减毒；大黄；肝肾毒性；恿醍；糅质；典型相关分析中图分类号：R283文献标识码:A文章编号:0513-4870(2009)08-0888-06InvestigationontheeffectofprocessingtothechemicalcontentsandthehepaticandrenaltoxicityofrhubarbbycanonicalcorrelationanalysisWANGJia-bo+,MAYong-gang+,ZHANGPing,JINCheng,SUNYu-qi,XIAOXiao-he\ZHAOYan-ling,ZHOUCan-ping(ChinaMilitaryInstituteofChineseMateriaMedica,302MilitaryHospital,Beijing100039,China)TheResearchCenterofXiyuanHospital,ChinaAcademyofChineseMedicalSciences,Beijing100091,ChinaAbstract:Inthisarticle,canonicalcorrelationanalysiswasusedtoexploretherelationshipbetweenthetoxicity-attenuatingeffectandthevariationofchemicalcontentsinrhubarbcausedbyprocessing.Withquasi-acutctoxicitytest,thedifferenceofhepaticandrenaltoxicitytomicewithintheprocessedmaterialsofrhubarbwasresearched・ThechemicalcontentsofanthraquinonesandtanninsinrhubarbweremeasuredbyUV-Visspectrophotometryandhighperformanceliquidchromatography.Theresultsshowedthatthereweretoxiceffectstoliverandkidneyinmiceafterrepeatedintragastricadministrationofrhubarbanditsprocessedmaterialsfor14daysatdosageof76gkg1.Andthetoxiceffectofprocessedmaterialswasmuchlowerthancrudedrug・Withcanonicalcorrelationanalysis,thesequenceofthehepaticandrenaltoxicityofchemicalcontentsinrhubarbwasfoundasfollow:totalanthraquinoneglycosides(AQGs)>tannins(Tns)>totalanthraquinones(AQs);aloe-emodin(AE)>physcione(Ph)>rhein(Rn)>emodin(Ed)>chrysophanol(Ch)andAEG>PhG>ChG>EdG>RnGofglycosyl-anthraquinone・1(couldbeconcludedthatprocessingwouldattenuatethetoxicityofcrudedrugofrhubarb・Thetoxicity-attenuatingeffectmightcorrelatedtothedeclineofthecontentsofbothanthraquinoneglycosidesandtannins,especiallythealoe-emodinglycosideandphyscioneglycoside・Theresultsalsosuggestedthattheserumalanineaminotransferase(ALT)andcreatine(CREA)收稿日期:2009-01-08.基金项冃：国家科技攻关专项课题“大黄不良反应与其复方制剂安全性的示范研究”(2004BA721A14).•共同第一作者.•通讯作者Tel/Fax:86-10-66933322,E-mail:pharmacy302@126.comwouldbeusefultomonitorthehepaticandrenaltoxicityofrhubarb.Keywords:toxicity-attenuatingeffectofprocessing;rhubarb;hepaticandrenaltoxicity;anthraquinones;tannins;canonicalcorrelationanalysis大黄在我国应用历史悠久，疗效广泛，现代药理研究表明其所含蔥服等成分具有致泻、止血、抗炎以及抑制癌细胞增殖和诱导凋亡等多种作川11】。大黄除应用于泻火通便外，近年来还常用于慢性肝炎、肾功能衰竭等疾病的长期治疗I5-，1]o然而，近年有报道大黄中成分对机体的肝肾功能有不良影响...