Akt介导炎症反应参与顺铂诱导的急性肾损伤-论文.pdf

《Akt介导炎症反应参与顺铂诱导的急性肾损伤-论文.pdf》由会员上传分享，免费在线阅读，更多相关内容在应用文档-天天文库。

1、·308·临床肾脏病杂志2014年5月第14卷第5期JClinNephrol，May2014，Vol_14No．5·实验研究·Akt介导炎症反应参与顺铂诱导的急性肾损伤李月强刘晓琴张炯杨娟陈关雪张春秀【摘要】目的目前急性肾损伤(acutekidneyinjury，AKI)发病率和死亡率较高，尤其是肾毒性药物所致AKI更加常见，为了更好地理解和干预AKI，本实验拟研究顺铂诱发的小鼠AKI的潜在发病机制。方法在小鼠成功构建顺铂诱发的AKI模型基础上，将1O只雄性C57BL／6(25—30)克小鼠随机分为2个组，每组6只(n：6)，分为对照

2、组和顺铂诱导的急性肾损伤模型组。模型组腹腔注射顺铂20mg／kg，对照组腹腔注射生理盐水(20mg／kg)，顺铂或生理盐水注射72h后处死小鼠，收集小鼠血清和肾脏标本。测定血清肌酐(SCr)和血尿素氮(BUN)。PAS染色后显微镜下观察肾脏形态学变化，Westernblotting免疫蛋白印迹分析蛋白激酶B(Akt)和磷酸化蛋白激酶B(p-Akt)的表达，实时定量(RT-PCR)检测白介素一6(IL-6)，干扰素-7(IFN一7)和肿瘤坏死因子(TNF_a)。结果与对照组相比，模型组SCr和BUN均明显升高，病理检查可见肾脏内肾小管上

3、皮细胞明显肿胀坏死、蛋白管型形成明显，还可观察到炎症细胞浸润明显增加。Westernblotting免疫蛋白印迹结果显示p_Akt表达明显上调，Akt表达不变，RT-PCR检测显示IL-6，IFN一和TNF-明显上调。结论在顺铂导致的小鼠急性肾损伤模型中，Akt的激活通过介导炎症反应参与了顺铂诱导的小鼠急性肾损伤。【关键词】顺铂；急性肾损伤；炎症InvolvementofAkt-mediatedinflammationincisplatin-inducedacutekidneyinjuryLIYue-qiang，LIUXiao-qin

4、g，ZHANGJiong，YANGJuan，CHENMei—aEue，ZHANGChun—xiu．DepartmentofNephrology，TongjiHospital，TongjiMedicalCollege，HuazhongUniversityofScienceandTechnology，Wuhan430030，ChinaCorrespondingauthor：ZHANGChun-xiu，E-mail：zhangchunxiu03@163．corn[Abstract]ObjectiveToexplorethepotential

5、mechanismofacutekidneyinjury(AKI)inducedbycisplatininmice．MethodsSixmaleC57BL／6mice(weighing25—30g)wererandomlydividedintotwogroups：controlgroup，andcisplatin-inducedAKIgroup．Thesemicewerekilledat72ndhafteradministrationofcisplatininjectionorsalineinjection(20mg／kg，i．P．)

6、．Thebloodsampleswerecol—leetedandmeasuredforthelevelsofserumcreatinine(SCr)andbloodureanitrogen(BUN)．ThepathologicchangesofrenaltissueswereobservedaccordingtOPASstaining．ThemRNAlevelsofIL6，IFN一andTNF-aweredetectedbyRT-PCR．TheexpressionofAktandp-AktwasexaminedbyWesternbl

7、otting．ResultsAscomparedwithcontrolgroup，thelevelsofSCrandBUNinAKIgroupweresignificantlyincreased．Renaltubularnecrosis，proteincast，andinflammatorycellsinfiltrationinAKIgroupweremarkedlydeteriorated，moreoverthemRNAlevelsofIL-6，IFN-7andTNF-aandtheexpressionofp-Aktweresign

8、ificantlyup-regulatedinAtKIgroupascomparedwithcontrolgroup．Buttherewasnosignificantdifferenceintheexpressionof