广防己配伍黄芪肾毒性的代谢组学研究

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1、广防己配伍黄芪肾毒性的代谢组学研究作者：梁琦　谢鸣　倪诚　颜贤忠　张艳霞【摘要】利用代谢组学技术研究大鼠口服广防己及其配伍黄芪水煎液后尿液代谢图谱的变化，探讨黄芪配伍广防己对肾脏的减毒作用。［方法］雄性wistar鼠24只随机分为正常对照组、广防己组、广芪组，每组8只。广防己组按8.1g/kg，广芪组按9.1g/kg灌胃给药，正常对照组灌服等体积蒸馏水。连续给药4w后，收集大鼠24h尿液，测定尿液1HNMR谱；取血做BUN、SCr检测；取肾脏行组织病理学检查。［结果］给药4w时，广防己组BUN、SCr显著升高(P<

2、;0.01），肾组织呈现明显的病理改变；广芪组SCr水平较广防己组明显降低(P<0.05），肾组织病变范围及程度较广防己组轻。尿代谢图谱经主成分分析表明，广防己组尿中柠檬酸、2酮戊二酸、马尿酸盐、葡萄糖含量降低；TMAO、肌酸·肌酐含量升高。广芪组上述代谢物的变化呈不同程度地减小。［结论］广防己给药4w可造成肾功能的明显损害，配伍黄芪有一定的对抗其损伤的作用。【关键词】广防己；黄芪；中药配伍；肾毒性；代谢组学；核磁共振；模式识别［Objective］Studythemetabonomicsprofileofint

3、heurinesamplesofratdosedwithdecoctionsofAristolochiafangchiand10it’scompatiblewithAstragaliradix.TofoundthattheinhibitioneffectonNephrotoxicityofAristolochiaefangchibycompatiblewithAstragaliradix.［Method］24MaleWistarratsweredividedtothreegroups,theGgroupwereadmin

4、istratedby8.1g/kg-1ofAristolochiafangchi,theGQgroupwereadministratedby9.1g/kg-1ofAristolochiafangchicompatiblewithAstragaliradix,andthecontrolgroupbyequalvolumeofdistilledwaterfor4weeks.Onthe4thweekend,urinewascollectedandtheir1HNMRspectrawereacquired,andthensub

5、jectedtodataprocessandprincipalcomponentanalysis(PCA,PLSDAorOSC).Bloodbiochemicalanalysisandhistopathologicalexaminationwerecarriedout.［Results］TheBUNandSCrofGgroupweremarkedlyhigherthanthoseofthecontrolgroup(P<0.01)withpathologicalinkidney.MatchingwithAstrag

6、aliradixdecreasedtheSCr(P<0.05)andmitigatedthekidneypathologicalofGgroup,comparedtocontrolgroup,theurinaryconcentrationsofcitrate,2oxoglutarate,Hippurate,GlucoseinGgroupdecreased,whiletheTMAOandCreatinine/Creatineincreased.ThosechangesofmetabolitesinGQgroupw

7、erelighterthanthatintheGgroup.［Conclusion］TheAristolochiafangchicaninducerenallesionasrevealedbythemetabonomicanalysisofraturinesamplesaswellasblood10biochemicalanalysisandhistopathologicalexaminations.CompatiblewithAstragaliradixhassomeinhibitioneffectonrenaltox

8、icityofAristolochiaefangchi.　　Keywords:AristolochiaFangchi;Astragaliradix;compatibility;nephrotoxicity;metabonomics;nuclearmagneticresonace(NMR);patternrecogni