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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JOURNALOFCLINICALREHABILITATIVETISSUEENGINEERINGRESEARCHDECEMBER9,2008VOL12,NO50POBOX1200,SHENYANG110004CNZGLCKFCOM9884DEPARTMENTOFORTHOPEDICS,FIRSTAFFILIATEDHOSPITALOFZUNYIMEDICALCOLLEGE,ZUNYI563003,GUIZHOUPROVINCE,CHINAWAQINGDE★,MASTER,DEPARTMENTOFORTHOPEDICS,FIRSTAFFILIATEDHOSPITALOFZUNYIMEDICALCOLLEGE,ZUNYI563003,GUIZHOUPROVINCE,CHINAFREE_NO1163COMRECEIVED20080715ACCEPTED20080822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_NO1163COM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,SOTHETREATMENTISNOTFAVORABLEOBJECTIVETOSTUDYTHEFEASIBILITYANDMECHANISMOFINTRAMEDULLARYINJECTIONWITHSALVIAMILTIORRHIZAFORPREVENTINGOFSTEROIDINDUCEDNECROSISOFTHEFEMORALHEADDESIGN,TIMEANDSETTINGRANDOMIZEDCONTROLLEDANIMALTRIALWASPERFORMEDATZUNYIMEDICALCOLLEGEBETWEENAPRIL2005ANDMAY2007MATERIALSTHIRTY6MONTHOLDHEALTHYRABBITS,HALFAMOUNTOFMALEANDFEMALE,WEIGHING25025G,WERERANDOMLYDIVIDEDINTOTHREEGROUPSN10CONTROL,MODEL,ANDPREVENTIONGROUPSMETHODSNORMALSALINEWASINJECTEDINTOTHECONTROLGROUPPREDNISOLONEWASINJECTEDINTOMODELGROUP,75MG/KG,TWOTIMESPERWEEKFOR8WEEKSGLUCOCORTICOIDINDUCEDANIMALMODELINTHEPREVENTIONGROUPWASINTRAMEDULLARYINJECTEDWITHSALVIAMILTIORRHIZA,0305CMBELOWTHETHIRDTROCHANTEROFTHEFEMUR,04ML/KG,TWICEAWEEKFOR8WEEKSMAINOUTCOMEMEASURESBLOODLIPIDSLEVEL,SERUMCALCIUMANDPHOSPHORUSWEREMEASURED;XRAY,EMISSIONCOMPUTERIZEDTOMOGRAPHICECTANDHISTOPATHOLOGYWEREPERFORMEDRESULTSTHESERUMCALCIUMANDPHOSPHORUSINMODELGROUPWEREREMARKABLYREDUCEDXRAYSHOWEDINHOMOGENEOUSDENSITYOFTHEFEMORALHEAD,WITHIRREGULARRADIOLUCENTAREA,OBSCURESTRUCTURESOFBONETRABECULA,BUTINTACTFEMORALHEADANDNORMALJOINTSPACETHEBLOODFLOWANDBLOODPOOLSHOWEDDECREASINGRADIOACTIVEDISTRIBUTIONOFTHEFEMORALHEAD,ANDLOCALCONCENTRATIONOFNUCLIDEINTHEDELAYEDPHASEINTHEMODELGROUPHISTOPATHOLGICALOBSERVATIONSUGGESTEDTHATTHECORTICALBONEWASTHINNED,WITHTHINBONETRABECULAANDIRREGULARARRANGEMENT,NECROSEDBONEMARROWANDPIMELOSISANDINCREASEDBONELACUNATHECALCIUMPHOSPHORUSPRODUCTOFPREVENTGROUPWASINCREASED;XRAYSHOWEDNORMALFEMORALHEADAPPEARANCEANDNORMALBONEDENSITYEXCEPTUNCLEARBONETRABECULAECTSHOWEDTHEDYNAMICANDSTATICIMAGESOFTHEPREVENTIONGROUPWERESIMILARASNORMALIMAGINGOFRABBITSINADDITION,HISTOPATHOLGICALOBSERVATIONSUGGESTEDTHERATEOFEMPTYLACUNAWASDECREASED,ANDBONETRABECULAMINIMALLYTHINNEDWITHORDEREDARRANGEMENTCONCLUSIONSALVIAMILTIORRHIZAINJECTIONPLAYSAGOODEFFECTIVEROLEINTHEPREVENTIONOFSTEROIDINDUCEDAVASCULARNECROSISOFFEMORALHEADTHROUGHIMPROVINGHEMORHEOLOGYANDREDUCINGRATEOFEMPTYLACUNAWAQD,ZHANGTH,LIUYPREVENTIVEEFFECTSOFINTRAMEDULLARYINJECTIONWITHSALVIAMILTIORRHIZAONSTEROIDINDUCEDNECROSISOFTHEFEMORALHEADZHONGGUOZUZHIGONGCHENGYANJIUYULINCHUANGKANGFU2008;125098849888CHINAHTTP//WWWCRTERCNHTTP//ENZGLCKFCOM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(25025)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75MG/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0305CM处由外向内上方穿G1849G2530注G1849丹参注射液,每G140304ML/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JG1025G3281组G13467工程研究G994临床康G3809,2008,125098849888HTTP//WWWCRTERORGHTTP//CNZGLCKFCOM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/RCODENZLKHAH9885WWWCRTERORG本文导读0引言股骨头缺血性坏死是由于不同病因破坏了股骨头的血供而造成的以骨小梁和骨髓坏死为特征的临床常见病,其发病率和致残率高,是骨科界三大难治症之一1。临床上分为创伤性和非创伤性两大类。非创伤性股骨头缺血性坏死的病因病理较复杂,其发病机制目前尚未完全阐明,包括皮质激素和酒精及全身性疾病,如系统性红斑狼疮、血小板减少性紫癜、炎症性肠炎及胶原性血管病等诱导的股骨头缺血性坏死,其中激素性股骨头坏死的发病率占非创伤性骨坏死的首位2。马在山3收治的2123例股骨头坏死病例中,激素性股骨头坏死占6232。治疗分非手术治疗与手术治疗两大类,但目前尚未有一种理想的治疗方法。实验以兔为实验G4557G16949,G2454G10043G17166G18267等4造G8181法诱导激素性股骨头缺血性坏死的G2172G10301G8181G3423,G6518G16764G1037G2454G8892G4568G9094骨髓G14120G1881G8892G4568G4557激素性股骨头缺血性坏死的G20056G19462G1328G11004及机制,为临床有G6940G20056G19462激素性股骨头缺血性坏死G6564供实验G1393G6466。1材料和方法设计G19555机G4557G10043G2172G10301实验,G13466G14002病理G4410G16278G4531。时间及地点实验于200504/200705在G17993G1053G2319G4410G19510完成。材料G1593G5259G4490兔30G2494,G19616G19608G2520G2334,6G7388G21848,G1319质G1833925G102025KG,由G17993G1053G2319G4410G19510G2172G10301实验中G5527G6564供。G4472G921322G1021G263,G6164有G2172G10301G3355在同一G7477G1226G991G2345G12560G20294G1871,G17902G20130,G7643G1946G20075G12902G20294G7021G2902G1871,G14270由G20290G8712。实验G17819G12255中G4557G2172G10301G3800G13634G12538G2524科G4410G6228术G181082006G5192G457G1863于G2904G5465实验G2172G10301的G6363导性G5859见G458的G16213G87265。实验方法造模及分组观察指标大体形态观察G8611G2620G12228G2172G10301G1319质G183392G8437,G17842G13505G16278G4531G2172G10301G8623发G1821G8913G5242、皮G991G14038G13950G2414G5242、G20147G8454、G1427、精G12082G10378G1929、G8975G2172G2476G2282及G1319G15932有G7092G5875G7591和G9303G11125G5785G1929及有G7092死G1141G727G2474股骨头G7114G16278G4531股骨头G3818G16278、质G3332、G14406G8913及G1863节软骨G14406G8913和G3818形。X射线摄片G6164有G2172G10301在第8G2620结束G7114,予2%盐酸利多卡因约2ML全麻生G6940后,将兔俯卧位固定于XG4568线摄片台上,摄双髋G1863节XG4568线正位片,G16278G4531股骨头形态、骨质密G5242、骨小梁G2476G2282、骨质疏松及G1863节间隙等影像G4410G2476G2282G5785G1929。发射型计算机断层扫描G6164有G2172G10301XG4568线摄片检查结束后G4557双G991肢骨行SPECT显像。血脂和血钙血磷的测定血G14038的测定G11004OLYMPUSAU2700G3423全G14270G2172生G2282分析仪,采G11004酶G2282G4410法测定血清三酰甘油和胆固G18267的浓G5242。采G11004HITACHI7170AG3423全G14270G2172生G2282分析仪测定血清钙磷的G8712平。组织病理学观察采集血G9094G7643本后,采G11004空气栓塞法G3800死G6164有G2172G10301,G2474双侧股骨头,G2474G7643本G7114,G8892G5859保护好作者介绍文章第二作者张天宏教授为硕士生导师,先后主持了省长专项资金课题“椎间盘突出症致痛机理的研究”以及省科技厅攻关项目“股骨头缺血坏死发生机制及治疗的研究”获遵义市科技进步三等奖,对股骨头缺血坏死疾病基础及临床研究颇有建树。负责实验的设计及实施工作。同行评价实验以兔为实验对象,参照贺氏造模法诱导激素性股骨头缺血性坏死的动物模型,探讨了丹参注射液骨髓腔内注射对激素性股骨头缺血性坏死的预防作用及机制,为临床有效预防激素性股骨头缺血性坏死提供了实验G4007G2156,G1260G1684G1043G2048G2149G3755,G1838G4075G1206骨G3833G1102G99骨G3691G3276G99骨坏死等G1407G2040G1383G99G1407G1034G2635验G4355G2915作用。偏倚或不足实验G1254G1186G3248用激素诱导的动物模型G3262G1102G1631的,G1260G2915G2087G2087G3262G4234G2905股骨头坏死模型,G3106G1765G1102G1631G1551制G1528G1766临床G3467G1316的进G4282G2905模型G3087G3262G2765G2383G1466G3775。G2087G1206血G4363G99血G3010G1569G2432G99X射G3756G99发射型计G3384机G1390G1034G3137G2637G1764G4518G4366病理G3888G1466G2635探讨骨坏死的发病机制G3262G1476G1064G2149G3755的,后G3875研究G3859进G4002步G3579G3167G4144骨G3833G1102G99骨G3691G3276G99骨坏死G3757关的G1618项G4375G947G1983G1033。健康家兔适应性喂养1周,精确称质量,随机分为3组,采用贺氏造模法造模6。对照组(N10)预防组(N10)臀肌注射生理盐水,每次032MG/KG盐质量,每周2次,共8周。肌注青霉素钠5万U/只和硫酸链霉素100MG/只,每周2次,共8周,以防感染。模型组(N10)臀肌注射醋酸泼尼松龙,每次75MG/KG,每周2次,共8周。肌注青霉素钠5万U/只和硫酸链霉素100MG/只,每周2次,共8周,以防感染。臀肌注射醋酸泼尼松龙,每次75MG/KG,每周2次,同时双侧股骨头在全麻下,采用髂骨穿刺针在股骨第三转子尖下方0305CM处由外向内上方穿入后注入丹参注射液,每侧04ML/KG,每周2次,共8周。肌注青霉素钠5万U/只和硫酸链霉素100MG/只,每周2次,共8周,以防感染。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POBOX1200,SHENYANG110004CNZGLCKFCOM9886WWWCRTERORG股骨头软骨面。将股骨头沿冠状面中间剖开,生理盐水冲洗干净后,放入体积分数为01的中性甲醛缓冲液中固定1周,5硝酸脱钙57D,流水冲洗24H,系列梯度乙醇脱水,常规石蜡包埋,作46ΜM连续切片,苏木精伊红染色,光学显微镜观察,读片区为软骨下区,观察股骨头骨小梁、骨细胞、髓腔及脂肪细胞形态、结构和数量的变化;高倍镜下任选10个视野,每个视野计数50个骨陷窝,分别数出空缺的骨陷窝数,求出百分比,取双侧平均值,求出空骨陷窝率。主要观察指标3组G4490G1832G15892脂、G15892钙G11979、XG4568G13459、G2469G4568G3423计G12651G7438G7041G4630G6207G6563及组G13467G11161理学G6363G7643的变化。设计、实施、评估者G4466G20576的G16786计、G4466G7057及G16792G1284G11013G1852体作G13785及G11468G1863G17753G2173G12197G4472G2339G2173G4448G6116。统计学分析G2520组计量数G6466G18331G11004X_G102SG15932G12046,G18331G11004G2345G3252G13044G7053G5058分G7524,G11004SPSS100G13491计软G1226G17839G15904数G6466G3800理。G13491计学G3800理G11013G12544G980作G13785G4448G6116。2结果21各组大体形态观察结果22各组X射线片结果G4557G10043组双侧股骨头骨G11394G17148G4448G6984,G3835小及形态G8503常,骨G4506度均G2260,骨小梁G9177G7236,G1863G14422间G19565G8503常,G16277G32821。G8181G3423组股骨头骨G17148G11107G7506,头G1881G4506度G993均,G2499G16277G3835小G993G980的G3230状G17891G1154区,G18108分骨小梁G8181G12958G993G9177,G1306股骨头G1457G6357G4448G6984,G1863G14422间G19565G8503常,G16277G32822。G20056G19462组G19512骨小梁G11065微G993G9177G3818,股骨头形态和骨G4506度均G6521G17829G8503常,G16277G32823。23各组发射型计算机断层扫描结果G4557G10043组G2172态G994G19757态G3282G1699G12046股骨头放G4568性分G5079均G2260、G4557G12228,G16277G32824。G8181G3423组股骨头G3324G15892流,G15892G8756G11468放G4568性分G5079G12244G11107,G5322G17843G11468放G4568性G5334常G8999G13870,G16277G32825。G20056G19462组G2172态G994G19757态G3282G1699G5062G6521G17829G8503常G1832G7692G13044放G4568性骨显G1699结G7536,G16277G32826。FIGURE1XRAYPHOTOGRAPHOFTHEFEMORALHEADINCONTROLGROUPAT8WEEKS图1对照组8周股骨头的X射线表现FIGURE2XRAYPHOTOGRAPHOFTHEFEMORALHEADINMODELGROUPAT8WEEKS图2模型组8周股骨头的X射线表现FIGURE3XRAYPHOTOGRAPHOFTHEFEMORALHEADINPREVENTIONGROUPAT8WEEKS图3预防组8周股骨头的X射线表现FIGURE4RADIONUCLIDEBONEIMAGINGOFCONTROLGROUPAT8WEEKS图4对照组8周放射性核素骨显像FIGURE5RADIONUCLIDEBONEIMAGINGOFMODELGROUPAT8WEEKS图5模型组8周放射性核素骨显像RIGHTRIGHTRIGHT对照组毛发光泽,活动好,反应灵敏,进食佳,至取材时体质量较实验前增长,皮下脂肪丰富。取材时见的股骨头外观未见变形,骨质坚硬,软骨面致密而光滑,不易剖开切凿。模型组毛发干枯无光泽,活动减少,反应迟钝,食欲欠佳,体质量持续性下降,皮下脂肪逐渐减少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