一氧化氮介导雌激素的骨形成增加作用

一氧化氮介导雌激素的骨形成增加作用 一氧化氮介导雌激素的骨形成增加作用 7582ISSN1671—5926CN21—1470/Ri4,14~w.zglcldcom中国临床康复2004年11县旦塑查塑塑 day.ZhongguoLinchuang2003;7(12):1766—7(ChinaJ 11GaoXM,ZhangBL,ShangHC,etal,Theprotectiveeffectoffufangdanshenfang pretreatmentonmyocardialischemicalreperfusioninjury.ZhongguoL/nchuang ,l加2003;7(12):1754—6(ChinaJ 12XuJ,HuangXJ,QiFL,eta1.Improvementofvascularendothelialfunctionby tuotaiandhuangqiinjectionincoronaryheartdiseasepatientsZhongguo L/nchuang,咖2004;8(9):1762—3(China) 红花注射液对原发性高血压患者血管内皮的 保护作用 孙宜萍,杨建芬,李蔚(上海交通大学附属第六人民医院老年科,上海 市200233) 孙宜萍,女,1945年生,浙江省镇海市人,汉族,1969年上海医科大学毕 业,教授,科主任,主要从事老年心血管疾病的研究. 摘要 背景:血管紧张素转换酶抑制剂和钙离子拮抗剂对原发性高血压内皮 受损的保护作用的研究已很深入,传统祖国医药在这方面的研究愈发 显示出其重要地位. 目的:观察红花注射液对原发性高血压血管内皮的保护作用. :随机开放实验方法进行前瞻性病例对照/随访研究. 地点,对象和干预:在上海交通大学附属第六人民医院住院及门诊患者 中,根据1999WHO/ISH高血压指南和中国高血压防治指南的诊断标 准,选取70例原发性高血压(2,3级,极高危)患者,随机分为红花注射 液组24例,丹参注射液组23例,对照组23例.红花注射液组予红花注 射液20mL静脉滴注.丹参注射液组予丹参注射液20mL静脉滴注.对 照组只予常规降压药治疗.观察3组研究对象用药前后血管收缩因子, 血管舒张因子的变化. 主要观察指标:3组患者用药2周前后血管收缩因子(内皮素,血栓素 2)和血管舒张因子【一氧化氮,6一酮前列腺素一F- (6一keton—prostaglandinFl..6-Keto—PGF~=)】的变化. 结果:三组患者用药前血浆内皮素,一氧化氮,血栓素2,6一酮前列腺素 一 F1(6一keton—prostaglandinF1,6一Keto—PGF1)的检测结果差异无显着性 意义(P>0.05).红花治疗组在治疗后内皮素明显下降,与对照组和 丹参组有显着差别(P<0.05);治疗后红花组与丹参组血栓素 [(307.9?12.9).(275.5?10.9)ng/L】均比治疗前【(369.5 ?11.5).(344.9?9.9)ng/L】低(P<0.05);治疗后红花组一氧化氮, 6一Keto—PGFl明显增加(P<0.05). 结论:红花具有抑制血管内皮素和血栓素,提高血管内皮一氧化氮和前 列环素作用,临床保护血管内皮功能疗效显着. 中图分类号:R544.1文献标识码:A文章编号:1671—5926(2004)33—7580—03 孙宜萍,杨建芬,李蔚.红花注射液对原发性高血压患者血管内皮的保护作用… 中国临床康复,2004,8l331:7580—2[www.zgtckf.com] (EditedbyWangD/SuD) ? BASICRESEARCH? Effectofnitrogenmonoxidemediatedwithestrogenonboneformation? - HuiTu,An-LiYang,Jing-YuanDu Yi—HuiTu.An—LiYang,DepartmentofOrthopaedics,CentralHospitalof YangpuDistrict,Shanghai200090,China Jing-YuanDu,DepartmentofOrthopaedics,UnionHospitalAffiliatedto Ton~iMedicalUnivemity,Wu_han43oo22,HubeiProvince,China Yi—HUiTu?,Male,HanNationality,Bornin1964inWuhanCity,Hubei Province,China,GraduatedfromTonalMedicalUniversityin1999,Doctor, CIIiefphysician.Researchdirection:spinesurgeryandosteoporosis. turoger45@hotmail_corn Telephone:+86—21—65690502Ext.266Fax:+86—21—65698O40 Received:2004—06—10Accepted:2004—08—02(05/NX) Abstract BACKGR0IJND:Protectivemechanismofestrogenonboneformatlonisnot clear.Nitrogenmonoxide(NO)inducedbyestrogenmayhaveacertaineffect onboneformation. oBJECTI,:Toinvestigatetheeffectsofestrogenictreatmentonlevelsof plasmanlIrate/nitriteinovariectomiedrats. DESIGN:Randomizedcontrolledtria1. SETTING:ThedepartmentofOrthopaedicsofCentralHospita1.Yangpu District,Shanghai. PA踟C?0ANTS:ThisexperimentwasperformedintheAnitaalExperi— mentalCenterofTongjiMedicalUniversity.At0tal0f36healthycleanfe— maleSprague-Dawley(SD)rats,aged3monthsold,weighing220—245g, wereprovidedbytheAnimalExperimentalCenterofTongjiMedicaluni— versity. ?TERVENTIoNS:TwelveSDratsweregivenbilateralovariectomycorn— pletely.asovariotomygroup;TwelveSDratsweretreatedwitIltheirbilateral ovaryexposedbutnotresected,ascontrolgroup,another12SDwerecarried outbilateralovariectomyandreceivedcutaneousinjectionof125Ixgben— ovocylineverytwoweeks,asestrogentreatedgroup. MLA】oUTCoM哐M哐ASURES:ExpressionofNOsyntheticenzymein bonetissuewasmeasuredwiththemethodofimmunohistochemistrystaining; 1'Ilebonemineraldensity(BMD)wasmeasul'edtIldualenergyX—ray;Bone morphologicalandmetrologicalmeasurementwasmadewithimageanalysis system;Thelevelsofplasmanitrate/nitriteweredetectedwitIlopticaldensity method. 弛sULTS:Ovariectomyinducedsignificantlythelevelsofplasmanitrate/ niIeIBMD.thevolnnleoftrabecularboneasweUasotherbonemoroho. 1ogicalandmetrologicalparametes.Sixweeksafteroperation,themean levelsofplasmaniRate/nltriteintheeontrolandovariectomygroupswere (22.4?1.7)p~mol/Land(16.2?3.7)p~mol/L,respectively;thevalueof BMDwere(0.245?0.030)g/cmand(0.189?0.030)g/cm:,respec— tively,volumeof11"abec~arbonewere(31.97?3.50)%and(17.14 ?4.20)%.respectively.1'Iledifferencesbetweenthetwogroupswassig? nificant(P<0.01).Estrogeninhibitedthesechangesinducedbyovariecto- my.Themeanlevelsofplasmanitrate/nitrite,valueofBMDandvolumeof trabecularboneintheestrogen—treatedgroupwere(21.9?3.5)p~mol/L (0.234?0.020)g/cm2and(26.53?1.63)%,respectively,whichhad significantincreaseascomparedtlIthoseinovariectomygroup(P<0.01), andthedifferenceswasnotsignificantascomparedwiththoseincontrol group(P>0.05).ImmunoreactivitysignalsofNOsynthesiswel3Bdetected osteoblasts.TheexpressionofimmunoreactivitysignalsofNOsvnthetic enzymeintheestrogen-treatedgroupwaftsignificantlystrengthenedascomo paredtlIthoseofovariectomygroup(P<0.01). CONCLUSION:EstrogenstimulatesboneformationbyinductingNOpro- duction.NOisamediatorwhichstrengthensestrogen—inducedboneformation. TuYH,YangAL,DuJYEffectofnitrogenmonoxidemediatedwithestrogenonbone formation.ZhongguoLinchuang2004;8l3317582—4(China) [www.zg]ckf.com】 INTRoDUCTIoN Itisthoughtthatlosinges~ogen'sprotectiveeffectontheskeleton playsanimpo~antroleinthedevelopmentofpostmenopausalosteo- porosis….111eimbalancebetweenboneformationandabsorptionin- ducedbytheresectionofovariumormalfunctionofovaryisassociated t}Iboneloss.whichcanbepreventedbyes~ogenreplacement therapy.Es~ogenpreventsbonelosspossiblybystimulatingbone formationandinhibitingboneabsorption,buttheconcretemechanisms ofestrogen'sprotectiveeffectonbeBeiSobscureThisexperimentis toinvestigatetheeffectofnitrogenmonoxide(NO)onestrogen—induced boneformationbymeasuringthechangesofthelevelsofplasmani- irate/nitritebeforeandafteres~ogentreatmentincastratedrats. MATERIA1SAND匝HoDS Experimenta1.a...n...1...m......a..—l—~andmaterials Atotalof36healthyfemlecleanSpragIle-Dawley(SD)mts,aged3 7584 1SSN1671—5926CN21—147O/R 删COIB~23385083@sineCOIB涂意辉,等.一氧化氮介导雌激素的骨形成增加作用 bonetissues.80astopreventtheboHelOSSinducedbyestrogen deficiency.Otsukaetal…1reportedthatNOplaysanimportant roleintlleregulationofosteoblastfunction.Otherreportsindicated thatthelevelofNOwassignificantlydecreasedinmenopausal women,andNOreducedboneabsorptionthroughretractingosteo- clastsinthepresenceofNOdonor.Estrogen-inducedboHefor- mationwasinhibitedintransgenicmicebeingdeftcientinNO syntheticenzmaticresponse{12]. TlliSexperimenti8todeterminethe effectofNOinestrogen.inducedboneformation. Plasmanitrate/nitritecanreflectendogenousNOproductinhumans andrats.Theresultsoftheexperimentshowedthatovariectomyin_ ducedboneloss.andcomparedtllcontrolgroup,BMDandbone morphometryparametersweresignificantlydecreasedintheo— variectomizedgroup.Ithadobviousosteoporosisfeatures.And meanwhile,thelevelsofplasmanitrate/nitriteweresignificantly decreased(P<0.01).Sixweeksafteroperation,themeanlevelsof plasmanitrate/nitrite,BMDandthevolumeoftrabecularbonein thecontrolandovariectomizedgroupshadsignificantdifferences(P <0.01).Treatmenttllestrogeninhibitedthemorphological changesinbonetissueandthedecreaseinthelevelsofplasmani— trate/nitriteinducedbyovariectomy.Themeanlevelsofplasmani- trate/nitrite.BMDandthevolumeoftrabecularboHeintheestro- gen-treatedgroupweresignificantlyincreasedascomparedwith thoseintheovariectomizedgroup(P<0.01),andthedifferences betweentheestrogen-treatedandcontrolgroupswasnotsignificant (P>0.05).TheresultssuggestedthatthedecreaseofNOindueed byovariectomyiscorrelatedtllboneloss;whileestrogenreplace- menttherapyincreasedtheNOproductafterovariectomysothatthe boneformationwasincreased.whichwasinaccordancewithother scholarsreports.,I'lleexpressionofNOsyntheticenzymaticactivity iswidelyinboneceilsandisstrongerintheestrogen?treatedgroup, whileweakerintheovariectomizedgroup.Itisthoughtthatbone protectiveeffectofestrogenisatleastpartiallymedicatedbythe increaseofNOsyntheticenzymaticexpression.theimprovementof NOsyntheticenzymaticactivityandtheincreaseofNO.NOsynthetic promoterpossessesanestrogenresponseelement,andestrogenmay upregulatetheexpressionofNOsyntheticenzymeinosteoblasts【. Inconclusion,estrogenstimulatesboneformationbyregulatingNO production.NOisamediator.whichcausestheincreaseinestro- gen.inducedboneformation.However.furtherstudiesarerequiredto surveytheeffectofestrogenonNOproductiononthebasisofNO syntheticmRNA.Furtherelucidationofthemechanismsofestrogenon boneformationmayimprovetheelinicaltreatmentofosteoporosis. REFERENCEs lTuYH.YangAL_Thevaleofheelandfreefemoralheadultrasoundme~uresin predictingfemoralneckfracture.ZhongguoM?【2003;7(24): 33o0一"CMna) 2~uelsMJ,GibsonRL,ColleyS.Roleofendothelialnitricoxidesynthaseine. strogen-inducedosteogenesis.Bone2o0l:29(1):24—9 3MillerGDivorcingEstrogen'8BrishtandDarkSides.Sc/ence2002;298(6): 723—4 4DengZL.AnH.Effectsoflowintensitypulsedultrasoundonbloodflowand vascularregenerationinhealingofosteoperoticfracture.Zhongg~w,lc^?,lg Kan~fu2004;8(15):2896—7(China) 5uXY.ChiYW.PeiLc11lePresentstateandprospectoftIIepreventionand treatmentofosteoperoticfractures.ZhongguoL/nchuang啦2004;8(12): 6 7 8 2324—5 CompstonJE.Sexsteroidsandbone.PhysiolRev2o0l:8l(2):419—7 ThYH.YangAL.Effectofpulseelectromagneticfieldonexpressionofin— sulin.1ikegrowthfactor-1inh,netissueofovariectomizedrata.zhoggu0Gn- chang,l2o03;7(15):2136—7(China) ChenDB.BirdIM,ZengJ.Membraneestrogenreceptor-dependentextraeelluar signal—regulatedkinasepathwayacuteactivationofendothelialnitricoxidesyn- thasebyestrogeninuterinearteryendothelialcells.Endocr/no/ogy2004;145 (1):ll3—25 FoxSW.ChambersTJ,ChowJW.Nitricoxidei8KnearlymediatoroftIIeinereasein h,neformationbymechanicalstimulation.AmJPhysiol1996;270(3):955—60 WimalawansaSJ.Restorationofovarieetomy-inducedosteopeniabynitroglye- erin.C口Ira2000;66(1):56—60 OtsukaE.HiranoK,MatsushitsS,eta1.Effectsofnitricoxidefromexogenous nitricoxidedonorsonoateoblastiemetabolism.EurJPharmacol1998;349(2): 345—50 ArmourKE,ArmourKJ,GallagIlerME,eta1.Defectiveh,neformationandan- abolicresponsetoexogenousestrogeninmicewelltargeteddisruptioninen- dotIIeUalnitricoxide.Endocrinology2o0l:142(3):760—6 TobiasJH.CompetonJE.Doeses~genstimulateosteoblastfunctioninpost- menopausalwomen?Bone1999;24(1):121—4 一 氧化氮介导雌激素的骨形成增加作用? 涂意辉.杨安礼,杜靖远(上海市杨浦区中心医院骨科,上海市 200090;同济医科大学附属协和医院骨科,湖北省武汉市430022) 涂意辉?.1964年生,湖北省武汉市人,汉族,1999年同济医科大学毕 业,博士,主任医师,主要从事脊柱外科和骨质疏松的研究. 摘要 背景:雌激素的具体骨保护机制目前尚不清楚,一氧化氮可能在雌激 素促进骨形成增加中起到一定的作用. 目的:探讨雌激素治疗对卵巢切除大鼠血浆硝酸盐/亚硝酸盐水平的影 响. 设计:随机对照的试验. 单位:上海市杨浦区中心医院骨科和同济医院大学附属协和医院骨 科. 材料:实验在同济医科大学动物实验中心完成,选用3个月龄清洁级健 康雌性sD大鼠36只,体质量220,245g,由同济医科大学动物实验中 心提供. 干预:12只sD大鼠完整切除双侧卵巢,设为卵巢切除组;另12只暴露 双侧卵巢而不予以切除,设为对照组;雌激素治疗组12只切除双侧卵 巢后即刻及后每隔2周皮下注射苯甲酸雌二醇125P-g. 主要观察指标:通过免疫组织化学染色方法检测一氧化氮合成酶在骨组 织中的达,双能x射线测定骨矿密度值,图象分析系统进行骨形态学计 量学测量,光密度法测定血浆硝酸盐/亚硝酸盐水平. 结果:卵巢切除导致血浆硝酸盐/亚硝酸盐水平及骨矿密度值,小梁骨体 积等骨形态学计量学参数显着下降.手术后6周,对照组和卵巢切除组平 均血浆硝酸盐/亚硝酸盐水平分别为(22.4?1.7),(16.2?3.7)p.mol/L; 骨矿密度值分别是(0.245?0.030)g/cm~和(0.189?0.030)g/em~;小梁 骨体积分别为(31.974-3.50)%和(17.144-4.20)%,两组之间差异均有 显着性意义(P<0.01).雌激素治疗抑制了卵巢切除导致的这些变化,雌 激素治疗组平均血浆硝酸盐/亚硝酸盐水平为(21.94-3.5)p.mol/L,骨矿 密度值为(0.2344-0.020)g/cm,小梁骨体积为(26.534-1.63)%,与卵 巢切除组比较,均有显着性升高(P<0.01);与对照组比较,差异均无 显着性意义(P>0.05).一氧化氮合成酶免疫活性信号在成骨细胞内 测得,雌激素治疗组一氧化氮合成酶信号较卵巢切除组也显着性增强 (P<0.01). 结论:雌激素通过诱导一氧化氮的产生而刺激骨形成,一氧化氮是雌激 素诱导骨形成增加的介导剂. 主词:雌激素类;软骨形成;一氧化氮 中圈分类号:R681文献标识码:A文章编号:1671—5926(2004)33—7582—03 涂意辉,杨安礼,杜靖远.一氧化氮介导雌激素的骨形成增加作用【jI.中国临床 康复,2004,8l33J:7582—4[www.zglekf.com] (EditedbyZhangFJ/SuD) 9Ol23