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·228·解放军医学杂志2003年3月第28卷第3期MedJChinPLAVoI28No3Mar2003 褪黑素对糖尿病大鼠肾脏的保护作用! 200003上海第二军医大学长征医院张立斌刘志民何金张慧石勇铨刘会敏 摘要研究褪黑素(MeI)对糖尿病大鼠肾功能和肾脏形态学改变的影响。3月龄SD大鼠予链脲佐菌素(STZ)腹腔注射,诱导糖尿 病模型。将大鼠随机分为组:正常对照组();糖尿病对照组();小剂量治疗组(,·);大剂量治疗 4CNDMMeIDM+MeI10.2mg/kgdMeI 组(,·)。予治疗周后,观察各组大鼠血脂、肾功能、尿蛋白排泄量和肾脏形态学改变情况。结果显示,治疗 DM+MeI25mg/kgdMeI8MeI 对糖尿病大鼠体重、血糖、胆固醇水平无显著影响,但可使血甘油三酯水平降低。MeI干预可使糖尿病大鼠尿蛋白排泄量减少。糖尿病大 鼠肾重/体重比值升高,肾小球面积增大,细胞增生,PAS阳性物质沉积。接受MeI治疗的大鼠上述改变显著减轻,其作用效果与用药剂量 呈正相关。研究表明,MeI能有效改善糖尿病大鼠的肾小球硬化和小球内细胞增殖,减轻肾脏肥大,对延缓糖尿病大鼠肾功能恶化有一定 作用。 关键词糖尿病;肾;褪黑素 中国图书资料分类号R363;R585 PROTECTIVEEFFECTOFMELATONINONKIDNEYINDIABETICRATS ZhangLiBin,LiuZhimin,HeJinetal.ChangzhengHospitaI,SecondMiIitaryMedicaIUniversity,Shanghai200003, China AbstractToinvestigatetheprotectiveeffectofmeIatoninonthekidneysofSTZ-induceddiaBeticrats,experimentaIdiaBeteswasinducedBy intraperitoneaIinjectionofstreptozotocin50mg/kginmaIeSprague-DawIeyrats(150~200g).Threedaysafterstreptozotocininjection,thediaBet- :(),;(),·-1·-1, icratswereassignedtooneofthefoIIowinggroups1DMuntreated2DM+MeI1meIatoninsuppIementat0.2mgkgdByga- ;(),·-1·-1,,, vage3DM+MeI2meIatoninsuppIementat5mgkgdBygavage.Thetreatmentcontinuedfor8weeks.PeriodicaIIyBodyweight BIoodgIucose,pIasmatrigIycerideandchoIesteroIIeveIsweremeasuredascIinicaIandBiochemicaIparameters;pIasmacreatinine,creatinine cIearanc(eCcr),urinaryproteinexcretionweredetectedasrenaIfunctionindexes;kidneyweight,gIomeruIararea,PASpositivearea,andceII countswereevaIuatedashistoIogicaIdamageindexes.MeIatonintreatmenthadnosignificanteffectsonBIoodgIucoseandpIasmachoIesteraI,But IoweredpIasmatrigIycerideIeveIindiaBeticrats.MeIatonintreatmentreducedurinaryproteinexcretion.UntiItheendoftheexperiment,there werenosignificantchangesinpIasmacreatinineIeveI,CcrindiaBeticrats.MeIatonintreatmentdecreasedkidneyweight/Bodyweightratio,re- ducedPASpositivearea,gIomeruIarceIIuIarnumBerandgIomeruIarareawhichwereincreasedinDMrats.TheprotectiveeffectsofmeIatoninwere moreoBvioseinhighdosagegroups.MeIatonintreatmentcanaggravategIo