环孢素A诱发的大鼠糖尿病模型的建立及其机制的探讨-论文.pdf

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1、·基础论著·环孢素A诱发的大鼠糖尿病模型的建立及其机制的探讨闫赋琴滕雅琴陈充抒牛玉坚徐春【摘要】目的建立环孢素A诱发的大鼠糖尿病模型，通过血清胰岛素水平、胰岛素敏感指数、胰岛病理改变探讨环孢素A升高血糖作用的机制。方法雄性sD大鼠20只【(89±10)朗随机等分为两组，每组10只。环孢素A组：环孢素25mg·kg。·d一；对照组：每日给予等量生理盐水，大鼠均在空腹(禁食水8h)时灌胃给药，用药1h后喂食。每周测量大鼠体重，每月监测大鼠空腹血糖和环孢素A的血药浓度。用药5个月后于空腹状态下将每组大鼠处死，心脏穿刺取血，4％多聚甲醛体内灌流取胰腺组织，放射免疫方法检测大

2、鼠血清胰岛素水平，胰腺组织行病理组织学观察，应用SPSS13．0统计软件分析对资料进行统计分析。结果给药4个月后，与环孢素A组平均血糖大于7mmol／L，说明环孢素A诱发大鼠糖尿病模型成功。与对照组相比，环孢素组大鼠的胰岛素抵抗指数均明显升高(P<0．05)，胰岛素分泌指数明显降低(尸<0．05)，环孢素组大鼠胰腺组织的胰导管均遭到破坏，胰岛细胞数量减少，且明显坏死、空泡化。结论环孢素A导致胰岛细胞坏死，减少胰岛素的分泌、增加胰岛素抵抗从而导致大鼠血糖升高。【关键词】疾病模型，动物；环孢素A；胰岛素；移植后糖尿病Theestabfishmentofcyclospor

3、ineinduceddiabetesmellitusmodelsinratsYANFu—qin。，TENGYa-qin,CHENChong-shu,NIUYu-jian,XUChun．*DepartmentofPharmacy,theArmedPoliceGeneralHospital,Beijing100039,ChinaCorrespondingauthor．"XUChun,Email：wjxuchun@sohu．corn[Abstract]ObjectiveToestablishcyclosporineAinduceddiabetesmellitusmodel

4、sinratsandtostudythemechanismsofelevatingbloodglucosebythelevelofseruminsulin，insulinsensitivityindexandisletpathologicalalteration．MethodsSDmaleratswererandomlydividedinto2groups．Theratsincyclosporinegroupwereadministratedwithcyclosporine25mg‘kg。‘d．whileTheratsincontrolgroupwereadmini

5、stratedwithequivalentdistilledwatereveryday．Eachgroupweretakenintragastricadministrationonanemptystomach(fasting8hours)andwerefedafteronehour．Theweightofratsweremeasuredeveryweek，fastingblood-glucoseandblooddruglevelofCsAweremonitoredeverymonth．Theratsofeachgroupwereexecutedonanemptyst

6、omachafter5months，gotbloodbycardiacpunctureandpancreatictissuebyinvivoperfusionof4％paraform，thelevelofseruminsulinweretestedbyradioimmunitymethod，pancreatictissuewereobservedinhistopathology，andSPSS13．0statisticalanalysissoftwarewasusedfordataanalysis．ResultsThefastingbloodglucoselevel

7、sincyclosporinegroupwerehigherthan7mmol／Lafter4months，whichindicatedthatcyclosporineinduceddiabetesmellitusmodelwasestablished．ARer5months，theinsulinresistanceindexincreasedsignificantly(P<0．05)，insulinsensitivityindexdecreasedsignificantly(P<0．05)，pancreaticductalofpancre~ictissuesw