PPAR-γ激动剂吡格列酮通过抑制炎症反应减轻顺铂诱导的小鼠急性肾损伤-论文.pdf

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1、·278·壁痘查生筮鲞第6期JClinNephrol，June2013，Vo1．13，No．6·实验研究·PPAR一激动剂吡格列酮通过抑制炎症反应减轻顺铂诱导的小鼠急性肾损伤张炯李俊华肖芳兰小勤裴广畅李月强刘蔚高红宇韩敏徐钢【摘要】目的研究过氧化物酶体增殖物激活受体(peroxisomeproliferator-activatedreceptor，PPAR)一激动剂吡格列酮对顺铂(cisplatin，CDDP)诱导的小鼠急性肾损伤(acutekidneyinjury，AKI)的可能保护作用及其机制。方法腹腔注射顺铂制备小鼠AKI模型。18只小鼠随机分为正常对照组(CT组)，AKI模型组(C组)

2、和吡格列酮治疗组(C+P组)。C组和C4-P组按25mg／kg给予顺铂处理。C+P组在顺铂注射前3d，连续三天给予吡格列酮灌胃。CT组给予生理盐水作为对照。顺铂或盐水处理72h后处死小鼠，收集血清和肾脏标本。测定血清肌酐和尿素氮，PAS染色后显微镜下观察肾脏形态学变化，同时通过Westernblot检测炎症指标诱生型一氧化氮合酶(induciblenitricoxidesynthase，iNOS)。结果与CT组相比，CDDP诱导C组血清肌酐及尿素氮明显升高，病理检查可见肾小管上皮细胞肿胀坏死、蛋白管型形成及炎症细胞浸润明显增加，同时炎症指标iNOS表达上调。与C组相比，C+P组血清肌酐、尿素氮

3、明显下降，肾小管上皮细胞肿胀坏死减轻，炎症细胞浸润减少，iN0S表达下调。结论PPAR-激动剂吡格列酮可通过抑制iNOS削弱炎症反应从而减轻顺铂诱导的小鼠急性肾损伤。【关键词】小鼠；顺铂；炎症Peroxisomeproliferator-activatedreceptor-?agonistpioglitazoneattenuatescisplatin-inducedacutekidneyinjurythroughinhibitinginflammationinmiceZHANGJiong，LJJun-hua，XIA0Fang，eta1．De-partmentofNephrology，Tongj

4、ihospital，TongjiMedicalCollegeofHuazhongUniversityofSci-enceand了nology，W

5、Il口430030，GhinaCorrespondingauthor：LIJun-hua，E-mail；lijunhua333@163．f[Abstract]ObjectiveToinvestigatepotentialprotectionandmechanismofperoxisomeprolifer—ator-activatedreceptor-7agonistpioglitazoneincisplatin-inducedacutekidneyi

6、niuryinmice．Methods18maleC57BL／6wererandomlydividedintothreegroups：Normalcontrolgroup(CT)。Cisplatin-inducedAKIgroup，Cisplatin-inducedAKItreatedwithpioglitazonegroup(C+T)．ThemiceinCgroupandC+Tgroupreceivedpioglitazone(35rag／kg)eitheraloneorbeforecisplatininjection．Pioglitazonewasadministeredthroughor

7、．algavageonceadayfor3days．Thesercewereputtodeathafter72hofcisplatinorsalineinjection，andthenthebloodsampleswerecollectedandmeasuredthelevelsofserumcreatinine(SCr)andUreanitrogen(BUN)．ThepathologyofrenaltissueswasobservedaccordingtoPASstainingandtheexpressionofinflammationmakeriN0Swasdetectedwithwest

8、ernblot．ResultsThelevelofSCrandBUNincisplatingroupwassignificantlyhigherthanthatinnornalcon-tmlgroup．Moreover，renaltubularnecrosis，proteincast，inflammatorycellirdiltmtion，andtheexpressionofiNOSWereall