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丹参骨髓腔内注射预防激素性股骨头坏死的可能性★.pdf

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丹参骨髓腔内注射预防激素性股骨头坏死的可能性★.pdf

中国组织工程研究与临床康复第12卷第50期2008–12–09出版JournalofClinicalRehabilitativeTissueEngineeringResearchDecember9,2008Vol.12,No.50P.O.Box1200,Shenyang110004cn.zglckf.com9884DepartmentofOrthopedics,FirstAffiliatedHospitalofZunyiMedicalCollege,Zunyi563003,GuizhouProvince,ChinaWaQingde★,Master,DepartmentofOrthopedics,FirstAffiliatedHospitalofZunyiMedicalCollege,Zunyi563003,GuizhouProvince,Chinafree_no1163.comReceived20080715Accepted20080822遵义医学院第一附属医院,贵州省遵义市563003瓦庆德★,男,1980年生,贵州省遵义市人,回族,2007年遵义医学院毕业,硕士,主要从事股骨头缺血坏死研究。free_no1163.com中图分类号R683文献标识码B文章编号167382252008500988405收稿日期20080715修回日期2008082254200807150009/GWA丹参骨髓腔内注射预防激素性股骨头坏死的可能性★瓦庆德,张天宏,刘毅PreventiveeffectsofintramedullaryinjectionwithsalviamiltiorrhizaonsteroidinducednecrosisofthefemoralheadWaQingde,ZhangTianhong,LiuYiAbstractBACKGROUNDThepathogenesisofavascularnecrosisofthefemoralheadisstilluncertain,sothetreatmentisnotfavorable.OBJECTIVETostudythefeasibilityandmechanismofintramedullaryinjectionwithsalviamiltiorrhizaforpreventingofsteroidinducednecrosisofthefemoralhead.DESIGN,TIMEANDSETTINGRandomizedcontrolledanimaltrialwasperformedatZunyiMedicalCollegebetweenApril2005andMay2007.MATERIALSThirty6montholdhealthyrabbits,halfamountofmaleandfemale,weighing2.5±0.25g,wererandomlydividedintothreegroupsn10control,model,andpreventiongroups.METHODSNormalsalinewasinjectedintothecontrolgroup.Prednisolonewasinjectedintomodelgroup,7.5mg/kg,twotimesperweekfor8weeks.Glucocorticoidinducedanimalmodelinthepreventiongroupwasintramedullaryinjectedwithsalviamiltiorrhiza,0.30.5cmbelowthethirdtrochanterofthefemur,0.4mL/kg,twiceaweekfor8weeks.MAINOUTCOMEMEASURESBloodlipidslevel,serumcalciumandphosphorusweremeasuredXray,emissioncomputerizedtomographicECTandhistopathologywereperformed.RESULTSTheserumcalciumandphosphorusinmodelgroupwereremarkablyreduced.Xrayshowedinhomogeneousdensityofthefemoralhead,withirregularradiolucentarea,obscurestructuresofbonetrabecula,butintactfemoralheadandnormaljointspace.Thebloodflowandbloodpoolshoweddecreasingradioactivedistributionofthefemoralhead,andlocalconcentrationofnuclideinthedelayedphaseinthemodelgroup.Histopatholgicalobservationsuggestedthatthecorticalbonewasthinned,withthinbonetrabeculaandirregulararrangement,necrosedbonemarrowandpimelosisandincreasedbonelacuna.ThecalciumphosphorusproductofpreventgroupwasincreasedXrayshowednormalfemoralheadappearanceandnormalbonedensityexceptunclearbonetrabecula.ECTshowedthedynamicandstaticimagesofthepreventiongroupweresimilarasnormalimagingofrabbits.Inaddition,histopatholgicalobservationsuggestedtherateofemptylacunawasdecreased,andbonetrabeculaminimallythinnedwithorderedarrangement.CONCLUSIONSalviamiltiorrhizainjectionplaysagoodeffectiveroleinthepreventionofsteroidinducedavascularnecrosisoffemoralheadthroughimprovinghemorheologyandreducingrateofemptylacuna.WaQD,ZhangTH,LiuY.Preventiveeffectsofintramedullaryinjectionwithsalviamiltiorrhizaonsteroidinducednecrosisofthefemoralhead.ZhongguoZuzhiGongchengYanjiuyuLinchuangKangfu2008125098849888Chinahttp//www.crter.cnhttp//en.zglckf.com摘要背景由于股骨头缺血性坏死的确切发病机制尚不清楚,其治疗方法尚不理想。目的观察丹参注射液骨髓腔内注射预防激素性股骨头缺血性坏死的可行性和机制。设计、时间及地点随机对照动物实验,细胞病理学观察,于200504/200705在遵义医学院完成。材料健康家兔30只,雌雄各半,6月龄,体质量(2.5±0.25)kg,随机分为对照组、模型组、预防组,每组10只。丹参注射液。方法对照组臀肌注射生理盐水。模型组臀肌注射醋酸泼尼松龙,每次7.5mg/kg,每周2次,共8周。预防组臀肌注射醋酸泼尼松龙制作糖皮质激素诱导激素性股骨头坏死动物模型,同时采用髂骨穿刺针在股骨第三转子尖下方0.30.5cm处由外向内上方穿g1849g2530注g1849丹参注射液,每g14030.4mL/kg,每周2次,共8周。主要观察指标观察3组家兔血g14038、血g19053g11979、X射g13459、发射型g16757g12651机g7041g4630g6207g6563g2462组g13467病理学g6363g7643的g2476g2282。结果模型组血清g19053和g19053g11979g1068g12227g7138g7186g19489g1314,X射g13459g12046股骨头g4506g5242不g3355,可g16277g3835g4579不g980的g3230g10378g17891g1154g2318,g18108分骨g4579g7765模g12958不清,g1306股骨头g1457g6357完g6984,g1863g14422g19400g19565g8503g5132g727发射型g16757g12651机g7041g4630g6207g6563g7186g12046股骨头在血g8981、血g8756g11468g6930射性分g5079g12244g11107,g5322g17843g11468g6930射性g5334g5132g8999g13870g727组g13467病理学观察g7186g12046,股骨头骨皮质g2476g15192,骨g4579g7765g2476细,g13479g7512g13022g1093,骨髓g7138g7186坏死和g14038g13950g2282,g12366骨g19531g12401g10587g7138g7186g3698g3822。预防组血清g19053、血清g19053g11979g1068g12227g2331g20652g727X射g13459g12046g19512骨g4579g7765g11065g5506不清外,股骨头g5430g5589和骨g4506g5242g3355g6521g17829g8503g5132g727发射型g16757g12651机g7041g4630g6207g6563g7186g12046动g5589g994g19757g5589g3282g1699g5062g6521g17829g8503g5132兔g7692素g6930射性骨g7186g1699g13479g7536g727组g13467病理学观察g7186g12046,骨g4579g7765g2476细不g7138g7186,g6502g2027g17751g16280g2029,g19531g12401内骨细胞g6980量g12257g7389g1955g4581,细胞g7692g3278g13565g17805g13870g10628g16949不g1017g18337,g12366骨g19531g12401g6980量g17751模型组g7138g7186g1955g4581。结论g3809方丹参注射液可g17902g17819g6925g2904血液g8981g2476学、g19489g1314g12366骨g19531g12401g10587g13792g1147生对股骨头缺血性坏死的预防作用。关键词股骨头g727缺血性坏死g727糖皮质激素g727髓腔内注射g727丹参g10938g5210g5515,g5364g3837g4451,g2028g8601.丹参骨髓腔内注射预防激素性股骨头坏死的可g14033性J.g1025g3281组g13467工程研究g994临床康g3809,2008,125098849888http//www.crter.orghttp//cn.zglckf.com基础医学瓦庆德,等.丹参骨髓腔内注射预防激素性股骨头坏死的可能性ISSN16738225CN211539/RCODENZLKHAH9885www.CRTER.org本文导读0.05模型组三酰甘油和总胆固醇均高于其他组P0.05各组间血清磷比较无统计学意义P0.05对照组、预防组两组血清钙磷乘积均升高,两组相比较无统计学意义P0.05,但与模型组比较均有显著性差异P0.05,见表3。3.88±0.69a3讨论g4625g12661g5062有大量的g1032g5214和g4466g20576g11752g12362,但g17816g1182股骨头g13582血性g3363g8527的g11842g2011g2469g11161g7438g2058g4590g993清g7982,g1032g5214防g8847g5049g1328的g5332g4649有很大的g3268g19602。g1363g11004g2172g10301模型g7171g980g12193g1427于g16760g16794和g2469g10628生g2641g12197学规g5471的g4466g20576g7053g8873和g6175g8585。g5326g12447模型的Figure6Radionuclideboneimagingofpreventiongroupat8weeks图6预防组8周放射性核素骨显像表1各组血清三酰甘油和总胆固醇比较Table1ComparisonofserumtriglycerideandtotalcholesterolTCamongthreegroupsx_±sControlModelPrevention1.27±0.476.50±0.63a1.85±0.78bGroupaP0.01,vs.controlgroupbP0.01,vs.modelgroup10910nTriglyceridemmol/LTCmmol/L1.35±0.343.88±0.69a1.82±0.48b表2各组血清钙、磷及其乘积比较Table2Comparisonoftheserumcalcium,serumphosphorusandcalciumphosphorusproductamongthreegroupsx_±sControlModelPrevention3.68±0.432.39±0.25a3.37±0.43bGroupaP0.01,vs.controlgroupbP0.01,vs.modelgroup10910nCalciummmol/LPhosphorusmmol/LCalciumphosphorusproduct2.24±0.152.28±0.142.26±0.158.21±0.835.45±0.77a7.59±0.91bFigure7Histopathologicsectionofcontrolgroupat8weeksHEstaining,40图7对照组8周病理组织切片苏木精伊红染色,40)Figure8Histopathologicsectionofmodelgroupat8weeksHEstaining,40图8模型组8周病理组织切片苏木精伊红染色,40Figure9Histopathologicsectionofpreventiongroupat8weeksHEstaining,40图9预防组8周病理组织切片苏木精伊红染色,40表3各组空骨陷窝率比较Table3Comparisonofpercentageofemptybonelacunaamongthreegroupsx_±sControlModelPreventionGroupaP0.01,vs.controlgroupbP0.01,vs.modelgroup10910nPercentageofemptybonelacuna9.42±0.7229.12±1.21a10.27±0.99b瓦庆德,等.丹参骨髓腔内注射预防激素性股骨头坏死的可能性P.O.Box1200,Shenyang110004cn.zglckf.com9888www.CRTER.org方法有单纯激素模型78、血清加激素模型910、内毒素加激素模型等11,且给药剂量和给药途径亦不尽相同。本实验大体形态观察结果示模型组动物毛发干枯无光,精神活动情况差,体质量持续性下降,皮下脂肪逐渐减少,甚至有1只兔死亡,说明大剂量激素可使实验动物的整个身体功能状况和免疫力明显下降。组织病理学观察结果示模型组股骨头骨皮质变薄,骨小梁变细,结构紊乱,骨髓明显坏死和脂肪化,空骨陷窝率明显增多,为29.12±1.21%。上述实验结果说明单纯激素能诱导股骨头坏死模型,本实验复制的动物模型是g6116功的。实验发g10628模型组骨小梁内不同g12255g5242的脂肪细g14002增g10995,g13945大,g13792骨细g14002明显减少,g17837g1135g15932g10628可能g994激素g1431使骨细g14002g2533脂肪细g14002g17728化有g1863。实验发g10628模型组骨髓g14120内大量的脂肪细g14002g3647g3634,g18108g2010g15713g2524为g8885状,g1866可能是股骨头g7101g7411坏死的g11464g6521g2419g3252。g20652脂血g11163g5751g13785血g9094g21667g9394性增g2065212,血小g7507功能明显g1142g178391320,g6937g4493g7143g14280股骨头的g9375g1871血g12661内血g7655形g6116,g1186g13792发g10995股骨头坏死。本实验结果示模型组血清g19053和g19053g11979g1068g12227明显降g1314,g994g4557g10043组和g20056g19462组相g8616有显g14891性差g5334,g15932明骨g11428大量g1014g3845,g19053g11979g8797g12227减少,g1186g13792导g14280g1114骨质g11107g7506,同g7114骨坏死g2530不能g5483g2052有g6940的g1474复和g18337g5326,加g17907g1114骨坏死g17839g12255。实验Xg4568g13459g10267示模型组股骨头骨质g11107g7506,可g16277g3230状g17891g1154g2318,g18108g2010骨小梁模g12958不清,g1306股骨头g1457持g4448整,无g3616陷,g6365Ficat13g2010g7411g4658g1122g7101g7411坏死模型g708g265g266g7411g709。骨g989g7114显g1699g708血g8981相、血g8756相、g5322g17843相g709g2465g7156骨的血g8981和g1207g16886情况,g4557股骨头坏死的g7101g7411g16798g7041g19762g5132g6947g587514,g1866g994Xg4568g13459、CT相g8616g17751,能g6564g208136个g7388发g10628股骨头坏死,g994MRI相g8616g1075能g3827g6564g2081g1120g989g2620发g10628病变15。g1306是发g4568型g16757g12651g7438g7041g4630g6207描g4658g1122功能性检查,多种疾病均能影响骨的放g4568性核素吸收,g6937特g5334性g17751差g6207描g18337叠及g1314空间g2010辨率亦可影响病灶范围的判定16。本实验结果示模型组股骨头在血g8981相,血g8756相放g4568性g2010布稀g11107,g5322g17843相放g4568性g5334g5132浓聚,放g4568性g2010布不均,g6947g5875性g17751g20652。实验通过骨髓g14120内注g4568给药取g5483g1114g17751好的g20056g19462g6940果,g15932明该给药途径能使局g18108血药浓g5242升g20652、作用g7114间g5322长,充g2010发挥g1114药物的作用。g3252髓g14120内毛细血g12661g17751丰富,g6937该给药途径还具有g10995物利用g5242g20652及吸收快等优点,减少g1114药物的全身用量,降g1314药物g4557g19762靶器官的毒副作用。同g7114,用骨穿针经皮行骨皮质穿刺,使g17751封闭的g14120隙被打开,骨内压降g1314,受压的血g12661g5483g2052缓冲,一定g12255g5242上改善g1114微循环,增加g1114股骨头的血g8981量。杨林17采用经股骨大g17728子下g2533股骨颈穿刺,行股骨头骨髓g14120内注g4568复方丹参注g4568g9094治疗能明显改善血g9094g8981变学,降g1314空骨陷窝率。本实验参考刘丹平等18报道的方法,结g2524大量的g20056实验认为穿刺点选在股骨第g989g17728子尖g2081下方0.30.5cm处,g994股骨轴g13459g611645°50°g1186外g2533内上方穿入的g6116功率g20652。4参考文献1ZhuSX.ChangshaHunanScienceTechnologyPress1999306朱盛修.股骨头缺血性坏死诊疗学M.长沙湖南科学枝术出版社,19993062ChenJW,QinSH.ShiyongGukeZazhi200394329331陈建文,秦泗河.激素性股骨头缺血坏死研究进展J.实用骨科杂志,2003,943293313MaZS.BeijingPeoplesMedicalPublishingHouse1994116117马在山.马氏中医治疗股骨头坏死M.北京人民卫生出版社,19941161174HeXJ,MaoLZ,WangKZ,etal.ZhonghuaGukeZazhi1992126440443贺西京,毛履真,王坤正,等.肾上腺皮质激素引起股骨头缺血性坏死的机制实验研究J.中华骨科杂志,1992,1264404435TheMinistryofScienceandTechnologyofthePeoplesRepublicofChina.Guidancesuggestionofcaringlaboratoryanimals2006093020080620.http//www.most.gov.cn/zfwj/zfwj2006/200512/t20051214_54389.htm中华人民共和国科学技术部.关于善待实验动物的指导性意见.2006093020080620.http//www.most.gov.cn/zfwj/zfwj2006/200512/t20051214_54389.htm.6LiuPL,XiaRY,ZhangSJ.ZhongguoJiaoxingWaikeZazhi200189889891刘培林,夏仁云,张士杰.股骨头缺血性坏死造模的实验研究J.中国矫形外科杂志,2001,898898917ChangW,ChengSH,SongYM.ZhongguoKangfuYixueZazhi2005208576578常巍,程少华,宋跃明.激素性股骨头坏死动物模型的诱导与观察J.中国康复医学杂志,2005,2085765788MastsuiM,SaitoS,OhzonoK,etal.Experimentalsteroidinducedosteonecrosisinadultrabbitswithhypersensitivityvasculitis.ClinOrthop1992277619ChenYH,YinHF,WangSL.ShandongZhongyiyaoDaxueZuebao2003273222223陈彦华,殷惠芬,王式鲁.马血清加激素诱导股骨头缺血性坏死动物模型的实验研究J.山东中医g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