糖皮质激素总结

1•甘草次酸对尿中a/b比值的影响指标 生理盐水 甘草酸 1IB-HSD的经典抑制剂甘草酸250mg-kg'1灌(咱L) _胃6匚天鼠尿中A/Lff较生理丽潮下降上4.1烷A 13.8±5.7点1±6*3'B 8.0±2,714.1±6.5A/B1.7iD.2\1.1±D.j/2•要不要提取微粒体提取和不提取的好处3.11B-HSD1存在于肝，肺，睾丸，脂肪，卵巢。NADP(H)依赖酶。主要催化可的松(E)失活为氢化可的松(F)。lip-HSD2存在于肾，结肠，胎盘，唾液腺。NAD依赖酶。催化氢化可的松失活(F)为可的松(E)。4•甘草次酸3-P-D-(Monoglucuronyl)-18-p-glycyrrhetinicacid,ametaboliteofglycyrrhetinicacidinhibitstheconversionofactivecortisoltoinactivecortisoneinthekidneys.Thisoccursviainhibitionoftheenzymebyinhibitingtheenzyme11-p-hydroxysteroiddehydrogenase.Asaresult,cortisollevelsarehighwithinthecollectingductofthekidney.Cortisolhasintrinsicmineralocorticoidproperties(thatis,itactslikealdosteroneandincreasessodiumreabsorption)thatworkonENaCchannelsinthecollectingduct.Hypertensiondevelopsduetothismechanismofsodiumretention.Peopleoftenhavehighbloodpressurewithalowreninandlowaldosteronebloodlevel.Theincreasedamountsofcortisolbindstotheunprotected,unspecificmineralocorticoidreceptorsandinducesodiumandfluidretention,hypokalaemia,highbloodpressureandinhibitionoftherenin-angiotensin-aldosteronesystem.Thereforelicoriceshouldnotbegiventopatientswithaknownhistoryofhypertension.3-葡萄糖苷酸-180-甘草次酸，是甘草次酸的一种代谢物，可以抑制有活性的氢化可的松转化为无活性的可的松。这种转化通过抑制110-HSD这种酶。结果，氢化可的松在肾集合管的水平偏高。最终导致~~~血压偏高。5.甘草次酸IC50

GlycyrrhetinicacidBufoarenarumstronginhibitionofisozymellbeta—HSD2GlycyrrhetinicacidCanisfamiliaris,Caviaporcellus一GlycyrrhetinicacidHomosapiens一GlycyrrhetinicacidHomosapiensinhibitsbothllbeta—hydroxysteroiddehydrogenaseandcarbonylreductaseactivitiesoftheenzymepotentlyGlycyrrhetinicacidHomosapiensisozymellbeta—HSDlinhibitor,residueTyr177isimportantinbinding,molecularmodelingGlycyrrhetinicacidMesocricetusauratus,Musmusculus,Rattusnorvegicus一6.110-HSD1和110-HSD2和甘草次酸的结构甘草次酸H0HH0H甘草次酸H0HH0H7.［甘草酸、甘草次酸18H差向异构体研究进展］摘要：甘草酸，是中药甘草的主要有效成分，其水解后的苷元称为甘草次酸。由于三铁皂苷母核18位手性碳原子（C18）构型不同，甘草酸和甘草次酸均有a0两种差向异构体。甘草具有多种药理活性，临床广泛用于抗炎和保肝解读等。再起对甘草酸、甘草次酸的研究大多没有将两异构体明确区分，但C18上的构型所引起的差异症日益受到关注。8浙江医科大学硕士学位论文］――a书草酸对豚鼠肾11B-羟基类固醇脱氢酶活性的影响摘要：本研究采用豚鼠离体和整体实验，研究了a-GA对110-HSD2的抑制作用a-GA对离体11B-HSD2的抑制作用。11B-HSD2动力学参数测定。花白两种豚鼠11B-HSD2体外活性的差异。a-GA对整体豚鼠HSD2活性的抑制作用。1.GA对离体11B-HSD2的抑制作用。花豚鼠肾脏皮质，制成匀浆液提取微粒体酶11B-HSD2，加入底物F进行反应，以F/E作为指标，研究了a-GA对11B-HSD2的抑制作用。2.11B-HSD2动力学参数测定。3.a-GA对整体豚鼠HSD2活性的抑制作用。三组豚鼠，分别腹腔注射生理盐水（SN）,a-GA（75、150、300mg/kg）和B_GA，连续15日收集第十五天的豚鼠尿液，用高效液相测定其中的E的含量以及E/F的比值；第16日取豚鼠血，测定血清钾离子浓度；取肾皮质，提取微粒体酶11B-HSD2,9./pubmed/7859916Cloningandtissuedistributionofthehuman11beta-hydroxysteroiddehydrogenasetype2enzyme.人体11B-HSD2的组织分布和克隆Theenzyme11beta-hydroxysteroiddehydrogenase(11betaHSD)isthoughttoprotectthenon-selectivemineralocorticoidreceptorfromoccupationbyglucocorticoids,andtomodulateaccessofglucocorticoidstoglucocorticoidreceptorsresultinginprotectionofthefetusandgonads.11betaHSD可以保护非选择性盐皮质激素受体AubiquitouslowaffinityNADP+dependentenzyme(11betaHSD1)andatissuespecific,highaffinityNAD+dependentform(11betaHSD2)of11betaHSDexist.WenowreporttheisolationofacDNAcodingforhuman11betaHSD2.ThenewisoformisNAD+dependent,exclusivelydehydrogenaseindirectionality,inhibitedbyglycyrrhetinicacidandmetabolizesthesyntheticglucocorticoiddexamethasone;itdisplaysKmvaluesforcorticosteroneandcortisolof5.1nMand47nM,respectively.Sequencealignmentshowsthat11betaHSD2shares35%identitywith17betaHSD2,butisonly14%identicalwith11betaHSD1.The11betaHSD2geneishighlyexpressedinkidney,colon,pancreasandplacentaandthemessageisalsopresentintheovary,prostateandtestis.Thesedatasuggestthat11betaHSD2playsanimportantroleinmodulatingmineralocorticoidandglucocorticoidreceptoroccupancybyglucocorticoids10./pubmed/20005656EnhanceddistributionandextendedeliminationofglycyrrhetinicacidinmiceliverbymPEG-PLAmodified(mPEGylated)liposome.AbstractArapidandsimplemethodofhigh-performanceliquidchromatographywithUVdetectorforthequantificationofglycyrrhetinicacid(GA)inmiceplasmaandtissueshasbeendevelopedandvalidated.一种快速简单的甘草次酸在小鼠血液和组织中的定量方法已经发展和建立。Withtheestablishedassaymethod,thepharmacokineticprofilesandtissuedistributionofGAindifferentformulationsarecomparedinmiceafterintravenousadministrationofthedrug(25mg/kg).随着这种方法的建立，在小鼠体内药物静脉注射甘草次酸药动学类型和组织分布已经建立。TheresultsshowedthatmPEG-PLAmodified(mPEGylated)GAliposome(PL-GA)significantlyprolongedthemeanresidencetime(MRT)ofGAinmiceplasmaandliver(MRT:0.43+/-0.13and1.72+/-0.11h,respectively)thanthenormalGAliposome(L-GA)(MRT:0.23+/-0.01and1.07+/-0.31h,respectively)andGAsodiuminjection(S-GA)(MRT:0.13+/-0.01and0.95+/-0.08h,respectively).mPEG-PLA修饰后的脂质体让GA在小鼠血浆和肝组织的停留时间比未修饰的要长。Moreover,PL-GAspecificallyincreasedGAuptakeinliver(AUC(O-infinity,)(liver)valueof1.6-foldand1.3-foldhigherthanthatforS-GAandL-GA,respectively)andreduceditsdistributionintoothertissuesafterdosing.然而，PL-GA增加了肝中的摄取比S-GA和L-GA在组织中的时间要长。Duetothesepharmacokineticproperties,itmaybepromisingtodevelopPL-GAfurtherasanewpharmaceuticalpreparationforGAonthetreatmentofvariouschronichepaticdiseases.11.Analysisandpharmacokineticsofglycyrrhizicacidandglycyrrhetinicacidinhumansandexperimentalanimals人体和实验动物体内甘草酸和甘草次酸药动学分析Glycyrrhizicacid(GZA)andglycyrrhetinicacid(GRA)canbedeterminedrapidlyandpreciselybyhigh-performanceliquidchromatography(HPLC)inbiologicalfluidsandtissuesfromexprimentalanimalsandhumans.甘草酸和甘草次酸可以通过液相来测定实验动物和人类的生物液体和组织。Fromplasmaandtissues,GZAandGRAareextractedbyorganicsolventsandtheextractscandirectlybeusedforHPLC.从血液和组织中，甘草酸和甘草次酸通过有机溶剂来提取，提取物可以直接用于液相。Frombileorurine,extractionanddeterminationofGZAandGRAaremorediffucultduetointerferingendogenouscompoundsandconjugationofGRAwithglucuronidesorsulfates.对于胆汁和尿液，甘草酸和甘草次酸的提取和测定更困难，来自于内源化合物的干扰以及甘草次酸同葡糖醛酸苷类以及硫酸盐类的干扰。ExtractionofGZAandGRAfromurineorbilecanbeperformedbyion-pairingfollowedbyextractionwithorganicsolventsorbysolidphaseextraction.GRAconjugatescanbedeterminedbychromatographicseparationorbypretreatmentwithp-glucuronidase.ThepharmacokineticsofGRAandGZAcanbedescribedbyabiphasi