中药调整性早熟儿童青春发育进程的机制研究(1)］目的：从神经内分泌调节及基因表达的角度，探讨调整性早熟儿童青春发育进程的滋阴泻火中药和益肾填精中药有效调节下丘脑垂体促性腺机能、促生长机能的作用机制。方法：青春期大鼠分别予以喂饲滋阴泻火中药或益肾填精中药。采用神经生物学实验方法（下丘脑推挽灌流、组织匀浆、脑片孵育及免疫组化法）检测下丘脑促性腺区促性腺激素释放激素（gonadotropinreleasinghormone,GnRH）的含量、脉冲释放频率与幅度，以及中枢氨基酸递质、神经肽Y及β内啡肽释放的变化；采用定量逆转录聚合酶链反应检测下丘脑GnRH、生长激素释放激素（growthhormonereleasinghormone,GHRH）、生长抑素（somatostatin,SS）、腺垂体卵泡刺激素（follicularstimulatinghormone,FSH）、黄体生成素（luteinizinghormone,LH）、生长激素（growthhormone,GH）、长骨干骺端胰岛素样生长因子Ⅰ（insulinlikegrowthfactorⅠ,IGFⅠ）基因及蛋白的表达水平。结果：滋阴泻火中药可明显抑制下丘脑促性腺区兴奋性氨基酸递质的释放，促进抑制性氨基酸递质、神经肽Y和β内啡肽的释放，使下丘脑GnRH神经元的功能活动降低，下调GnRH、FSH及LH基因的表达水平，上调下丘脑SS基因的表达，并下调垂体GH及长骨干骺端IGFⅠ基因的表达，从而明显抑制下丘脑垂体的促性腺机能及促生长机能。益肾填精中药则可明显抑制下丘脑促性腺区神经肽Y的释放，使下丘脑GnRH神经元的功能活跃，上调GnRH、FSH及LH基因的表达，下调下丘脑SS基因的表达，上调垂体GH及长骨干骺端IGFⅠ基因的表达，从而明显促进下丘脑垂体的促性腺机能及促生长机能。结论：滋阴泻火中药和益肾填精中药可通过调整机体的神经内分泌调节机制，调整下丘脑GnRH、SS，腺垂体FSH、LH、GH及长骨干骺端IGFⅠ基因的转录，有效调节下丘脑垂体的促性腺机能及促生长机能。这可能是滋阴泻火中药和益肾填精中药可有效调整性早熟患儿青春发育进程及改善骨骼发育的主作用机制。［关键词］中药;青春期，早熟;神经递质;神经肽Y;β内啡肽;下丘脑垂体性腺轴;生长抑素生长激素胰岛素样生长因子Ⅰ轴EffectsofChineseherbalmedicineonmodulatingthecourseofpubertydevelopmentinchildrenwithprecociouspubertyABSTRACTObjective:ToexplorethetherapeuticeffectsofZiyinXiehuoRecipe(ZYXHR)fornourishingyinandloweringfireandYishenTianjingRecipe(YSTJR)fornourishingkidneyandreplenishingessenceonregulatingthegonadotrophicandsomatotrophicfunctionsofhypothalamicpituitaryaxis,andtorevealthemechanismsofZYXHRandYSTJRinmodulatingthecourseofpubertaldevelopmentofchildrenwithprecociouspuberty.Methods:ThepubertalratswerefedwithZYXHRorYSTJRfor30days,andtheparametersofratsweremonitoredasthefollowings:Thecontentofgonadotropinreleasinghormone（GnRH）,thefrequencyandamplitudeofGnRHimpulsereleasing,thereleasingamountsofaminoacidneurotransmitters,andneuropeptideY(NPY)andβendorphin(βEND)inthegonadotrophicareaofthehypothalamusweredetectedwithneurobiologicalmethods(pushpullperfusion,homogenate,incubationofbrainslices,andimmunohistochemicalstaining).ThelevelsofgeneandproteinexpressionsofGnRH,growthhormonereleasinghormone(GHRH)andsomatostatin(SS)inhypothalamus,andfollicularstimulatinghormone(FSH),luteinizinghormone(LH)andgrowthhormone(GH)inadenohypophysisaswellasinsulinlikegrowthfactorⅠ(IGFⅠ)inmetaphysisweredeterminedwithrealtimereversetranscriptionpolymerasechainreaction(RTPCR).Results:TheZYXHRcouldreducetheactivityofGnRHneuronsinhypothalamusthroughinhibitingthereleaseofcentralexcitingaminoacidneurotransmitters,whereaspromotingthereleaseofcentralinhibitingaminoacidneurotransmitters,NPYandβENDingonadotrophicareaofhypothalamus.TheexpressionlevelsofGnRH,FSHandLHmRNAsweredownregulatedwhiletheexpressionlevelofSSmRNAinhypothalamuswasupregul...
