ezrin蛋白在糖尿病肾病鼠肾小球的表达及活性维生素d对其的影响

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1、Ezrin蛋白在糖尿病肾病鼠肾小球的表达及活性维生素D对其的影响作者：杨媛媛，邹敏书余健聂国明罗莉漫徐洪涛赵林双何威逊【摘要】目的：观察Ezrin蛋白在糖尿病肾病(DN)大鼠肾小球的表达以及活性维生素D[1,25(OH)2D3]对其表达的影响。方法:Wistar大鼠随机分为对照组和糖尿病肾病模型组;后者经腹腔注射链佐脲菌素(STZ)诱导DN大鼠模型，再随机分DN组和1,25(OH)2D3组。1,25(OH)2D3组皮下埋置渗透性微量泵，给予1,25(OH)2D30.03ng/g·d-1，连用8周。检测大鼠血糖(Glu)、肾重/体

2、重(KW/BW)、24h尿蛋白(24hUP)、血肌酐(Scr)、尿足细胞(UPC)。采用间接免疫荧光检测肾小球Ezrin蛋白的表达与分布。WT1免疫组化染色检测每个肾小球足细胞数目。结果：与对照组相比，DN组Glu、KW/BW、24hUP、Scr、UPC显著升高;肾小球Ezrin表达显著下降，足细胞数目减少。DN组与1,25(OH)2D3组Glu水平无显著性差异，1,25(OH)2D3组KW/BW、24hUP、Scr、UPC较DN组显著降低;而肾小球Ezrin表达及足细胞数目显著增加。对照组Ezrin蛋白荧光染色沿肾小球毛细血管壁

3、均匀线型分布;DN组呈不连续的粗颗粒样分布;1,25(OH)2D3组部分呈短线型荧光。Ezrin表达荧光强度与肾小球足细胞数目呈正相关(rs=0.51，P<0.01)，与24hUP、UPC呈负相关(rs=0.43，0.45，P<0.01)。结论：1,2512(OH)2D3可减少DN鼠肾小球Ezrin的表达，减少足细胞脱落，维持肾小球足细胞数量。【关键词】足细胞;活性维生素D;Ezrin;糖尿病肾病;大鼠　　[ABSTRACT]Objective:Toobservetheeffectof1,25Dihydroxyvi

4、taminD3(1,25(OH)2D3)ontheexpressionofEzrininglomeruliofratswithdiabeticnephropathy(DN).Methods:Wistarratswererandomlydividedintotwogroups:controlgroupandDNmodelgroupwhichwasinducedbyperitonealinjectionofstreptozotocin(STZ).Afterthesemodelsweresuccessfullyestablished,the

5、ywererandomlydividedintotwogroups:DNgroupand1,25(OH)2D3group.1,25(OH)2D3groupwasembeddedwiththeosmoticminipumpforgiving0.03ng/g-1·d-11,25(OH)2D3for8weeks.Bloodglucose(Glu),theratioofkidneyweight/bodyweight(KW/BW),24hoururinaryprotein(24hUP),serumcreatinine(Scr)anduri

6、narypodoctye(UPC)weremeasured.TheexpressionanddistributionofEzrininglomeruliwasdetectedbyindirectimmunofluorescence.PodocytenumberperglomeruliwasdeterminedbyWT1immunohistochemistry.Results:Comparedwithcontrolgroup,thelevelofGlu,KW/BW,24hUP,Scr,UPCinDNgroupweresignifican

7、tlyincreased.TheexpressionofEzrininglomerulistatisticallydecreased.12Averagenumbersofpodocytesperglomeruliwasdramaticallyreduced.TherewasnosignificantdifferenceofGlubetweenDNand1,25(OH)2D3group.KW/BW,24hUP,Scr,UPCweresignificantlylowerin1,25(OH)2D3groupthaninDNgroup.Th

8、eexpressionofEzrinandthenumbersofpodocytesperglomeruliin1,25(OH)2D3groupwerehigherthanthoseinDNgroup.I