浅论左旋精氨酸对糖尿病大鼠的肾脏保护作用.docx

浅论左旋精氨酸对糖尿病大鼠的肾脏保护作用
【摘要】目的：探讨左旋精氨酸(Larginine，LArg)对链脲佐菌素(streptozotocin，STZ)诱导的糖尿病大鼠肾脏保护作用及机制。方法：建立STZ诱导的糖尿病大鼠模型,随机分为糖尿病模型组(DM组)和DM4周后LArg治疗组(LArg组),并以正常组作对照。观察8周后,测定各组大鼠尿白蛋白排泄率(UAER)、血肌酐(SCr)和血尿素氮(BUN)，光镜观察肾组织形态。检测血清和肾皮质中氧化亚氮(NO)、超氧化物歧化酶(SOD)及丙二醛(MDA)含量，测定肾脏线粒体膜电位及肿胀度。结果：与DM组相比,LArg组大鼠UAER，SCr，BUN显着降低(),肾脏病理形态得到一定改善;血清和肾皮质中NO及SOD含量显着升高(,)，MDA显着降低();肾脏线粒体膜电位显着升高()，肿胀度趋势增强。结论：左旋精氨酸对糖尿病大鼠肾脏的保护作用可能与增加NO合成，同时保护肾脏线粒体的功能有关。【关键词】左旋精氨酸;糖尿病肾病;氧化亚氮;线粒体[Abstract]Objective:ToexploretherenoprotectiveeffectofLarginineonstreptozotocininduceddiabeticratsanditspotential：DiabeticmodelswereinducedbyintraperitonealinjectionofstreptozotocinSTZinr+ats.Modelswererandomlydividedintotwogroups:DMgroup(nontreateddiabeticmodelrats)andLArggroup(diabeticmodelratstreatedwithLarginineafter4weeks).Thenormalnondiabeticratswereasthecontrolexcretionofurinaryalbuminexcretionrate(UAER),serumcreatinine(SCr)andserumureanitrogen(BUN)weredetectedafter8weeks.Morphologicalchangesofkidneywereobservedbyopticsmicroscope.Thelevelsofnitricoxide(NO)，theactivityofsuperoxidedismutase(SOD)andmalondialdehyde(MDA)inserumandrenalcortexweredetected;kidneymitochondrialmembranepotentialandmitochondrialswellingweremeasuredinthedifferentgroups.Results：ComparedwithDMgroup,theexcretionofUAER,SCrandBUNinLArggroupweresignificantlydecreased(),whiletheabnormalpathologicalchangeswereimproved;thelevelsofNOandtheactivityofSODinLArggroupwerealsosignificantlyincreased(,),thelevelsofMDAweresignificantlyreduced();thekidneymitochondrialmembranepotentialwassignificantlyelevated()andmitochondrialswellingwasreinforced.Conclusion：LarginineprotectsthekidneysduringdiabeticmodelratspossiblybyincreasingthelevelsofNOandimprovingthefunctionofmitochondria.[Keywords]Larginine;diabeticnephropathy;nitricoxide;mitochondrial糖尿病肾病(diabeticnephropathy，DN)是糖尿病最严重的慢性并发症之一，至今其发病机制尚未完全阐明。氧化应激主要由活性氧簇(reactiveoxygenspecies，ROS)介导，在DN启动和发展过程中起着重要作用。在病理状态下线粒体呼吸链发生断裂，成为ROS生成的主要来源[1]。氧化亚氮(nitricoxide,NO)是新型的生物信息传递体，具有舒张血管、松弛血管平滑肌和抑制内皮细胞增殖等功能，是具有生物活性的自