6肾切除大鼠早期模型中p38MAPK的动态变化.doc

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1、6肾切除大鼠早期模型中p38MAPK的动态变化【摘要】目的:研究5/6肾切除大鼠模型中p38MAPK磷酸化的动态表达情况。方法:82只雄性SD大鼠分为两组：5/6肾切除模型组72只，假手术对照组10只。模型组造模完成后，分别于肾切除早期（术后1/2h、1h、3h、6h、12h、1d、2d、4d）相应时间点处死，每组9只，假手术组于术后12h处死，称量各组体重及残余肾重，计算肥大指数；下腔静脉取血留取血清测定血肌酐（Scr）、尿素氮（BUN）；以Westernblotting免疫印迹法检测肾皮质磷酸化p38MAPK活性的表达情况；以病理光镜和电镜观察肾小球

2、、肾小管及肾间质组织形态学及超微结构的变化。结果:模型组与对照组相比，肾脏呈代偿性肥大，肥大指数增高（P<0.05），Scr和BUN升高（P均<0.01）。免疫印迹法显示5/6肾切除术后1/2h、1h、3h、6h、12h磷酸化p38信号呈递增趋势，尤以12h信号最强，之后信号减弱，2d时几乎不可见，4d有较弱的信号，假手术组未见明显信号。光镜下，发现肾小球有轻度系膜细胞增生，基质增宽不明显，肾小管偶有轻度变性，间质偶有炎性细胞浸润。电镜下，偶见足突局灶融合。结论:5/6肾切除大鼠在造模完成后12h时磷酸化p38MAPK表达最强。【关键词】5/

3、6肾切除p38MAPK信号转导磷酸化Abstract:Objective:Toinvestigatethedynamicexpressionofphosphorylating-p38inthe5/6subtotalnephrectomized(STNx)ratmodel.Methods:Eighty-twomaleSprague-Dawleyratswererandomlydividedintotwogroups:STNxgroup(n=72)andshamgroup(n=10).RatsinSTNxgroupweresacrificedinearlyn

4、ephrectomyathalfofanhour,1hour,3hour,6hour,12hour,1day,2dayand4day,9ratsforeach;ratsofshamgroupweresacrificedat12hour.Thebodyweight,kidneyweightweremeasuredandthekidney/bodyweightratiowascalculatedindifferentgroups.Serumcreatinine(Scr)andbloodureanitrogen(BUN)weredetermined.Theex

5、pressionsofphosphorylating-p38weremeasuredwithWesternblottinginrenalcortex.Thehistomorphologyandultrastructureoftherenalglomerulus,tubuleandinterstitiumwereobservedunderlightmicroscopeandelectronmicroscope.Results:ThekidneywereaugmentedforcompensationinSNTxgroupandthekidney/bodyw

6、eightratioinSNTxgroupwashigherthanthatoftheshamgroup,thesameastheScrandBUN(P<0.01).Westernblottingdisplayedthesignalofphosphorylating-p38wasincreasinggraduallyfromhalfofanhourto12hourafternephrectomy,especiallythehighestat12hour,thenthesignalweakened,signalalmostdisappear2days

7、laterandrecorveredtotenuitysignal4dayslater.Almostnoexpressionofphosphorylating-p38wasshownintheshamgroup.Itwasdisplayedunderthelightmicroscopetherewerelittleproliferation7ofmesangialcellsinrenalglomerulus,therewaslittledegenerationintherenaltubule,andlittleinflammatorycellularin

8、filtrationintherenalinterstitium.Thatpod