姜黄素抗顺铂肾毒性作用及其机制研究..docVIP

姜黄素抗顺铂肾毒性作用及其机制研宄 ：张英黄维义王顺蓉陈蓉 】目的探讨姜黄素抗顺铂所致大鼠肾损害的作 用及其机制。方法选择48只雄性Wistar大鼠，随机分为I， II，III，IV，V组，分别行第1次腹腔注射：生理盐水、CM N30mg/kg、CMN30mg/k g+锌原13卜淋IXlOmg/kg，8h 后，从 I， IV, V组中各任选6只鼠处死，检测HO 1蛋白表达与活 力。余鼠再行第2次腹腔注射：生理盐水，C丽20mg/kg+顺 钻6mg/kgo顺钻6mg/kg, 5d后处死，检测血肌酐、尿素氮、 肾脏系数、肾组织超氧化物歧化酶活力及谷胱甘肽和丙二醛 含量。结果顺铂可明显升高肾组织氧化应激水平并严重损伤 肾脏的结构和功能，姜黄素仅有较弱的直接抗顺铂肾毒性作 用，但用姜黄素预处理上调HO 1蛋白表迗及活力能显著增 强其抗顺铂肾毒性作用；反之，用ZnPPD（抑制HO 1活力 则可消除姜黄素抗顺铂肾毒性作用。结论姜黄素主要通过上 调HO 1蛋白表迗有效拮抗顺铂所致的氧化应激性肾损伤。 关键词】顺铂；姜黄素；血红素氧合酶 1;氧化 应激；肾毒性 StudyonthePr otectiveEffectandM echanismofCurcumin onCisplatin induce dNephrotoxicity Ab stract : ObjectiveTo investigatetheprot inducednephrot oxicityinratsandthepossiblemechanism s. Methods48malewis tarratswererandoml ydividedinto5group s : groupI(n=12),gro upll (n=6),groupIII (n=6),groupIV (n=12 ),groupV (n=12). Rat srecEivedintraperi toneallyinjectionf orthefirsttimeresp ectivelywithsaline (groupl,groupll,gr oupIII),CMN30mg/kg (groupIV)，CMN30mg/ kg+Zincprotoporphy rinIX(ZnPPIX)10mg/ kg(groupV). 8hoursl ater ， halfratsingro upl,groupIV,groupV wereki1ledtoanalys erenalHO IprotEIne xpressandratsrecei vedtheintrapariton eallyinjectionfort hesecondtimerespec tivelywithsaline(g roupl),Cisplatin6m g/kg+CMN30mg/kg(gr oupIII)andcisplati n6mg/kg(groupll,gr oupIV,groupV). 5day slater,alltheanima lswerekilledtomeas urethebloodcreatin in(Cr),ureanitroge n (BUN)andanalyseth erenalsuperoxidedi smutase(SOD)activi ty,glulathion(GSH) andmalondialdehyde (MDA)contentandhis dincreasetherenalolanddamageseriouslconstructionandonl (MDA)contentandhis dincreasetherenalo landdamageseriousl constructionandonl otectiveeffectagai ducedtherenalprote creasedsignificant regulate renalHO topathologicalcoul xidativestressleve ytherenalhistology yhasslightdirectpr nstthecisplatin-in ctiveeffectwouldin lybypretreatmentwi thCMNtoup lproteinle velandconsiderably attenuatedbyinhibi tingHO lproteinact ivitywithZnPP IX . Con clusionCMNcanprote ctagainstcisplatin inducedoxidatives tressrenalinjuryby indueingHO 1. Keywords: Cispla