实验性骨质疏松模型骨组织中核因子表达特征及其意义

目的 探讨核因子NF-KBP50、NF-KBP65在骨质疏松发病过程中的意义。方法选用4个月龄雌性BALB／C小鼠随机分假手术对照组（CON组）和去卵巢骨质疏松模型组（OVX组）,术后第12周测量全身骨密度后处死,取股骨下端用ABC免疫组织化学、原位杂交方法测定骨组织中核因子的蛋白含量及表达水平并进行细胞定位。结果OVX组与CON组相比,骨密度下降,股骨骨小梁稀疏、成骨细胞数目减少而破骨细胞数目增多;免疫组织化学染色结果显示,NF-kB P50、NF-kB P65蛋白在模型组和对照组均有阳性表达,主要位于骨小梁周边成骨细胞、骨细胞及骨髓细胞胞浆中,OVX组蛋白含量均高于CON组,且与骨密度呈负相关（P〈0．01或P〈0．05）;原位杂交结果表明,OVX组NF-kB P50 mRNA、NF-kB P65 mRNA表达显著高于CON组（P〈0．05）。结论骨质疏松骨组织及骨髓中核因子的蛋白含量及表达水平升高,在骨质疏松骨微环境中的表达异常并与骨密度明显相关。     

口服淫羊藿苷可提高大鼠的峰值骨密度和骨质量

目的研究口服淫羊藿苷(Icariin,ICA)是否能提高大鼠的峰值骨密度和骨质量,起到预防骨质疏松症的作用。方法 1月龄雌性健康SD大鼠随机分为两组,每组12只。服药组每日灌服25 mg/kg淫羊藿苷,对照组(CON)灌服给予等体积蒸馏水。每周监测大鼠体重。每月检测实验鼠的骨密度,3个月后处死所有大鼠。取血测血清骨钙素(OC)和抗酒石酸性磷酸酶5b(TRACP 5b)的含量。取双侧股骨和胫骨分别进行骨密度检测、μCT扫描和生物力学评价。剥离心、肝、胃、肾、肾上腺和子宫后称重,计算器官指数,并做常规病理学检测。结果两组大鼠的体重始终无显著性差异(P0.05);各脏器的器官指数均无明显差异,病理学观察未见异常改变。第1、第2月的全身骨密度无明显差别(P0.05),但3个月后,ICA组显著高于CON组,股骨骨密度存在相同趋势(P0.05);ICA组的血清OC水平升高,而TRACP 5b含量下降(P0.05);μCT检测结果是:ICA组的骨体积百分率、骨小梁厚度和骨小梁数量均高于CON组,但骨小梁分离度和模型系数显著低于CON组(P0.05);股骨最大载荷、弹性模量和屈服强度均是ICA组显著高于CON组(P0.05)。结论口服淫羊藿苷可通过抑制骨吸收而促进骨形成,提高大鼠的峰值骨密度和骨质量,对预防各种原因引起的骨质疏松及骨质疏松性骨折具有十分重要的意义。     

葛根素和白藜芦醇对青年大鼠峰值骨量的影响研究

目的:比较葛根素、白藜芦醇单体与二者的复合药物对大鼠峰值骨量的影响。方法 :选取雌性SPF级Wistar大鼠40只,体重109.45～119.44 g,平均115.87 g,大鼠适应3 d后采用随机数字表法将其分为4组,每组10只,分别为空白对照组(CON组,每日灌胃等体积的蒸馏水),葛根素组(PR组,每日灌胃15.4 mg/kg葛根素),白藜芦醇组(RES组,每日灌胃8.4 mg/kg白藜芦醇),复合药物组(P+R组,每日灌胃8.4 mg/kg白藜芦醇+15.4 mg/kg葛根素复合药)。每7 d监测1次大鼠体重,每月检测1次大鼠全身骨密度。3个月后处死全部大鼠。采用双能X线骨密度仪检测股骨和椎骨离体骨密度;采用万能材料试验机分析骨生物力学;采用VG染色分析骨形态计量学;采用ELISA试剂盒检测血清骨代谢指标及用Micro-CT扫描仪扫描股骨微结构。结果:各组大鼠在实验期间的体重变化无统计学意义;骨密度结果显示:与CON组比较,其余3组股骨和椎骨骨密度均显著升高,且R+P组显著高于PR组和RES组。股骨三点弯曲和椎骨压缩试验结果显示:与CON组相比,其余3组股骨和椎骨最大载荷值均显著升高,且P+R组高于PR组和RES组,而各组间弹性模量值无统计学意义;股骨VG染色结果显示:与CON组相比,其余3组骨小梁数目显著增加,分离度明显减低,且R+P组明显优于PR组和RES组,而各组间骨小梁厚度无显著变化。Micro-CT扫描重建图结果显示:与CON相比,其余3组股骨骨小梁结构紧密,数目较多,分离度小,连续性好,且R+P组显著优于RES和PR组;Micro-CT扫描指标结果显示:与CON组相比,其余3组股骨骨小梁数目(trabecular number,Tb.N)、骨小梁厚度(trabecular thickness,Tb.Th)显著增加,骨小梁分离度(trabecular spacing,Tb.Sp)显著降低,且差异具有统计学意义(P0.05),且R+P组显著优于RES和PR组。血清生化指标结果显示:与CON组相比,其余3组血清中骨钙素(osteocalcin,OC)水平均升高,抗酒石酸酸性磷酸酶5b(TRACP 5b)含量均下降,差异具有显著性,且P+R组显著高于PR组、RES组,而TRACP 5b含量无显著变化。结论:葛根素与白藜芦醇单体按1∶1比例组合而成的复合药在提高青年大鼠峰值骨密度和骨质量,增强骨生物力学性能,促进成骨细胞的矿化成熟,抑制破骨细胞骨吸收方面的药效显著优于葛根素和白藜芦醇单体的作用,表明中药复方或复合药将作为预防和治疗骨质疏松的新途径。     

联合补充大豆异黄酮和钙预防去势大鼠骨质疏松的实验研究

目的 研究联合补充大豆异黄酮和钙对去卵巢大鼠骨质疏松的预防作用。方法 将50只3月龄SD雌性大鼠摘除卵巢后按体重随机分成5组：假手术对照组、手术对照组、大豆异黄酮组（40mg／kgBW）、钙组（100mg／kgBW）、钙＋大豆异黄酮组（Ca100mg／kgBW＋SI40mg／kgBW）。连续灌胃饲养3个月后测定大鼠血清骨钙素，左侧股骨测定骨密度和骨钙含量、右侧股骨进行骨组织形态学计量分析。结果 Ca＋SI组血清BGP水平和股骨骨密度均高于其他去卵巢各组（P〈0．05），但低于Sham组（P〈0．05）；Ca＋SI组大鼠股骨的骨钙含量与Ca组、Sham组差异均无统计学意义；在去卵巢各组大鼠中手术对照组、大豆异黄酮组和钙组大鼠的骨小梁数目和骨小梁厚度显著减少，骨小梁间距明显增宽，与钙＋大豆异黄酮组相比有显著差异（P〈0．05）。结论 与单独补充大豆异黄酮或钙相比，大豆异黄酮与钙的联合应用能够更有效地预防去卵巢大鼠骨质疏松的发生。     

蓇密牌钙片对大鼠骨密度的影响研究

目的研究瞢密牌钙片对大鼠骨密度的影响。方法选用雌性Wistar大鼠50只，随机分成5组；每周量身长；给予该产品4周后，进行3天代谢实验；实验结束时，进行股骨骨密度测定和骨钙含量的测定。结果低、中剂量实验组的身长和身长净增加值显著高于低钙对照组（P〈0．05或P〈0．01）。各剂量实验组大鼠股骨中心矿物质含量和骨密度显著大于低钙对照组（P〈0．01或P〈0．05），高剂量实验组大鼠的股骨中心矿物质含量和骨密度显著高于碳酸钙对照组（P〈0．05）。高剂量实验组大鼠的股骨远心端骨矿物质含量和骨密度显著大于低钙对照组（P〈0．01）。中、高剂量实验组大鼠的股骨钙含量及总钙量显著大于低钙对照组（P〈0．01）。中、高剂量组、碳酸钙对照组大鼠钙的表观吸收率显著低于低钙对照组（P〈0．01）。中、高剂量实验组和碳酸钙对照组大鼠钙的存留率显著低于低钙对照组（P〈0．01）。结论认为瞢密牌钙片有增加大鼠骨密度的作用。     

OPG基因敲除小鼠骨质疏松情况的研究

目的研究护骨素（Osteoprotegerin，OPG）基因敲除纯合子小鼠（homozygous OPG knockout mice，OPG^-1- mice）骨质疏松发生情况，为OPG^-1-小鼠骨质疏松模型的应用提供依据。方法非频密繁殖法获得OPG^-1-小鼠，PCR技术进行OPG基因表型鉴定。16周龄OPG^-1-子代小鼠和16周OPG野生型小鼠各10只，采用双能X线骨密度测量仪（DEXA）测定全身骨密度（Bone mineral density，BMD）、万能材料试验机测定股骨生物力学强度；骨组织形态计量学分析L5椎体骨小梁结构；实时荧光定量PCR检测L1椎体骨组织中BMP-2、Runx2 mRNA表达水平。结果OPG^-1-子代小鼠和亲代纯合子小鼠表现出相同的OPG基因缺失表型。与同龄野生型小鼠比较，16周龄OPG^-1-小鼠全身骨密度、股骨承受最大载荷、股骨结构刚度、腰椎椎体骨小梁数目、腰椎椎体骨小梁厚度显著下降（t=5．740，6．069，6．859，6．891，3．558，P〈0．01）；股骨承受破裂载荷、腰椎椎体骨小梁体积分数下降（t=3．157，3．329，P〈0．05）；股骨承受载荷后的最大位移、破裂位移显著增加（t=-3．868，-3．276，P〈0．01）；腰椎椎体骨小梁分离度增加（t=-2．575，P〈0．05），腰椎椎体Runx2 mRNA表达升高（t=-3．738，P〈0．05）；腰椎椎体中BMP-2 mRNA表达升高不明显，差异无统计学意义（t=-1．589，P〉0．05）。结论OPG^-1-小鼠表现出明显的骨质疏松，是一种理想的骨质疏松模式动物。     

鹿瓜多肽对去卵巢大鼠骨密度、股骨生物力学及松质骨中BMP2表达的影响

目的鹿瓜多肽（松梅乐）注射液肌注对去卵巢大鼠骨密度、股骨生物力学及松质骨中BMP2表达的影响。方法将8月龄未经产雌性二级SD大鼠30只，随机分为假手术组（SHAM）组、去势组（OVX）、去势＋鹿瓜多肽（OVX＋CCP）组。OVX＋CCP组大鼠术后第1天开始给药，术后20周处死各组大鼠．应用双能X线吸收仪（DEXA）测量各组大鼠股骨粗隆、股骨干中点及第3～5腰椎中点的骨密度（BMD）；应用INSTRON1195电子拉伸试验机检测股骨生物力学性能；利用免疫组织化学染色及图像分析方法对各组大鼠松质骨切片图像进行灰度分析，观察鹿瓜多肽注射液对OVX大鼠松质骨中BMP2表达的影响。结果（1）OVX与SHAM组比较，灰度值降低明显（P〈0．01），而OVX＋CCP组灰度值较去势组降低（P〈0．01），表明OVX大鼠松质骨中骨小梁周围及髓腔中BMP2表达阳性细胞数明显多于SHAM组；而OVX＋CCP组骨小梁周围及髓腔内BMP2表达阳性细胞数多于去势组，且染色加深。（2）与SHAM组相比，OVX组股骨近端、股骨干、腰椎BMD明显降低（P〈0．01）；OVX＋CCP各部位BMD高于去势组（P〈0．01），但未达到SHAM组水平（P〈0．01）；（3）与SHAM比较，去势组大鼠股骨最大载荷、桡度、最大应力、弹性模量均明显下降（P〈0．01），治疗组上述指标高于去势组（P〈0．01），接近对照组水平（P〉0．05）。结论鹿瓜多肽注射液可以抑制和延缓骨质疏松的形成，对雌激素缺乏引起的骨质疏松具有预防作用。     

血清骨代谢标记物对预测类风湿关节炎关节破坏的意义

目的：探讨血清骨代谢标记物与RA患者关节破坏的相关性。方法选取140例住院RA患者,90例同期健康人作为研究对象。采用DEXA测定RA者腰椎（ L1～L4）及股骨上端骨密度值,根据T值分为正常骨量、低骨量、骨质疏松组3组;另根据双手X线结果显示关节破坏程度分为Ⅰ、Ⅱ、Ⅲ、Ⅳ期组;同时检测患者血清CTX、25（ OH） D、TRACP－5b、PTH、血钙、血磷、抗CCP抗体、RF、CRP、ESR。结果 RA组TRACP－5b、CTX水平明显高于健康对照组（Z＝－2．747,－4．809,P＜0．01）,25（OH）D水平明显低于健康对照组（Z＝－6．152,P＜0．001）;TRACP－5b与病程、关节压痛个数、CTX呈正相关（r＝0．193, r＝0．189, r＝0．196,P＜0．05）,随着疾病活动度的加重,TRACP－5b水平呈现递增趋势,且骨质疏松组TRACP－5b水平高于正常骨量组,但未达统计学差异;CTX与关节肿胀个数、25（OH）D呈正相关（r＝0．215, r＝0．192,P＜0．05）,其水平在疾病重度活动组明显高于中低度组;X线Ⅰ期组患者与其他各组相比年龄较小,病程较短,关节破坏程度轻;Ⅰ期、Ⅱ期组骨质疏松患病率明显低于Ⅲ期、Ⅳ期组（ P＜0．05）;骨量丢失随年龄增长、病程的延长、疾病活动度的加重而增加。结论骨代谢标记物与RA患者关节破坏有一定的相关性,联合检测多种骨代谢标记物可望预测关节破坏的程度。     

孕激素对去势血雌性大鼠骨密度及骨形态计量作用的初步研究

目的：了解孕激素对去势雌性大鼠骨密度及骨形态计量作用。方法：50只6月龄Wistar雌性大鼠随机分为5组：假手术组和卵巢除组、卵巢切除后分别加官宫黄体酮2mg组、安宫黄体酮20mg组和倍美力组。手术后7d喂药，用药后3个月处死。测定各组大鼠子宫 湿重、全身及股骨骨密度并取大鼠椎骨、胫骨组织切片进行形态计量分析。结果：两组孕激素组子宫湿重与卵巢切除组相同，均显著低于假手术组与倍美力组（P＜0．001）。假手术、雌、孕激素组全身骨密度测定均大于卵巢切除组（P＜0．05）。各组股骨骨密度无显著差异。组织切片观察显示，假手术与倍美力组骨小梁粗壮、饱满、结构完整；卵巢切除组则纤细、断裂、完整性差。孕激素组与骨小梁结构优于卵巢切除组但不及假手术及倍美力组。计量分析显示孕激素组椎骨骨小梁面积明显大于卵巢切除组（P＜0．05），但低于倍美力组（P＜0．05）。胫骨骨小梁面积与卵巢切除组相仿，均明显低于假手术和倍美力组（P＜0．05）。孕激素2mg与20mg组间无明显差异。结论：两组剂量的安宫黄体酮对卵巢切除大鼠骨质疏松均有一定防治作用，但从骨组织形态计量分析，其作用较弱，与结合雌激素相比，尚不足以维持骨量。     

丹参酮Ⅱ A对生长期大鼠骨密度及骨形态计量学影响的研究

目的研究丹参酮ⅡA对生长期大鼠骨密度及骨形态的影响,并探讨其可能的机制,对其预防与治疗骨质疏松症的疗效作出初步判断。方法 1月龄雌性Wistar大鼠30只,随机分为丹参酮ⅡA组[11 mg/(kg·d),n=10]、淫羊藿苷组[阳性对照,25 mg/(kg·d);n=10]和正常对照组(相同体积蒸馏水,n=10)。每两周称取一次体重,每月用双能X射线骨密度仪检测全身骨密度;若组间全身骨密度差异有统计学意义,处死所有实验动物。测定椎骨和右侧股骨的离体骨密度;品红-苦味酸染色(van-gieson,VG)进行骨形态分析;ELISA法检测血清抗酒石酸性磷酸酶5b(TRACP 5b)和骨钙素(osteocalcin,OC)的水平。结果大鼠的体重比较差异无统计学意义(P0.05);第1个月全身骨密度无明显差异(P0.05),第2个月给药组全身骨密度均显著高于对照组,与对照组相比,丹参酮ⅡA组和淫羊藿苷组大鼠全身骨密度、椎骨骨密度、股骨骨密度、骨小梁数目、骨小梁厚度、骨小梁面积和血清OC均有所增加,差异均有统计学意义(P0.05);而骨小梁间隙和血清TRACP 5b均减小,差异具有统计学意义(P0.05)。丹参酮ⅡA组和淫羊藿苷组差异没有统计学意义(P0.05)。结论丹参酮ⅡA可通过提高大鼠骨密度及骨质量来预防与治疗OP,对探索抗骨质疏松中药单体新药有非常重要的意义。     

低频脉冲电磁场对青年大鼠峰值骨量的影响研究

目的:比较1 h和1.5 h下低频脉冲电磁场对生长期大鼠骨质量的影响。方法 :选取4周龄30只雄性SPF级SD大鼠,体重(115.8±1.5) g,采用随机数字表法将大鼠分为对照组、1 h组和1.5 h组,每组10只。对照组大鼠在电磁场装置中每天静置1.5 h,1 h组和1.5 h组均使用50 Hz 0.6 mT强度脉冲电磁场每天分别干预大鼠1 h和1.5 h。每2周称量大鼠体重,检测大鼠全身骨密度值,6周后处死大鼠检测右侧股骨和腰椎离体骨密度和生物力学值。ELISA法测定血清骨钙素(osteocalcin,OC)和抗酒石酸酸性磷酸酶5b(tartrate-resistant acid phosphatase 5b,TRACP 5b)浓度。品红-苦味酸染色后观察其右侧胫骨微组织结构,IPP 6.0软件对骨小梁相关参数进行分析。结果:各组不同时间点大鼠体重和脏器指数比较差异无统计学意义。骨密度结果显示:与对照组相比,6周时1.5 h组的全身骨密度、股骨和椎骨离体骨密度显著增加;且1.5 h组股骨和椎骨骨密度高于1 h组。股骨三点弯曲和椎骨压缩试验结果显示:与对照组相比,1.5 h组股骨和椎骨最大载荷值明显增加,且1.5 h组股骨最大载荷值显著高于1 h组,而3组弹性模量值比较差异无统计学意义。血清生化指标结果显示:与对照组相比,1.5 h组大鼠OC水平明显提升,且显著高于1 h组,而各组TRACP 5b值比较差异无统计学意义。骨形态计量学分析显示:与对照组相比,1 h组骨小梁厚度、数目和分离度不具有统计学差异,而1.5 h组骨小梁厚度和骨小梁数目均显著增加,骨小梁分离度显著下降;1.5 h组较1 h组骨小梁厚度和数目也明显增加,分离度减小。结论:50 Hz 0.6 mT低频脉冲电磁场干预大鼠1.5 h可以有效提高青年大鼠峰值骨密度和骨微结构,增强骨生物力学性能,促进大鼠血液中骨形成标记物的浓度,表明脉冲电磁场可作为预防和治疗骨质疏松的良好方法。     

50 Hz 1.8 mT正弦交变电磁场对生长期大鼠骨密度的影响研究

目的 :探讨50 Hz 1.8 mT正弦交变电磁场(sinusoidal electromagnetic fields,SEMFs)对SD大鼠骨密度(bone mineral density,BMD)的影响。方法 :将30只1月龄体重为(110±10)g的SD大鼠随机分为正常对照组和电磁场组,各15只。分别给予对照组50 Hz 0 mT和电磁场组50 Hz 1.8 mT强度正弦交变电磁场干预,1.5 h/d,每周称取体重1次,每天监测进食量变化,6周后腹腔注射麻醉大鼠并用双能X骨密度检测全身骨密度,处死后检测股骨骨密度及椎体骨密度;ELISA法测定血清骨钙素(Osteocalcin,OC)和血清抗酒石酸性磷酸酶5b(tartrate resistant acid phosphatase5b,TRACP 5b);剥离肝、肾、子宫称重,计算器官指数并做HE切片做常规病理学检测分析。结果:与对照组相比,电磁场组大鼠各周体重、每日进食量未见明显变化;2、4周后全身骨密度无明显变化,6周后全身骨密度及离体股骨和椎骨骨密度显著增加;血清OC表达量显著增加,血清TRACP 5b表达量显著降低;子宫、肝脏、脾脏HE染色未见病变,脏器指数无异常。结论:50 Hz 1.8 mT正弦交变电磁场能通过提高骨形成降低骨吸收相关因子的表达,从而提高青年大鼠的峰值骨密度,为临床电磁场预防骨质疏松的研究奠定基础。     

Effects of genistein on vertebral trabecular bone microstructure,bone mineral density,microcracks, osteocyte density,and bone strength in ovariectomized rats

Until now, the effects of phytoestrogen on bone in both women and ovarian hormone-deficient animal models of osteoporosis have remained uncertain. We have aimed here to investigate the effect of genistein (GEN) on trabecular bone quality in ovariectomized (OVX) rats. Forty 7-month-old female Sprague-Dawley rats were randomly divided into the following four groups: OVX, sham-operated (SHAM), treated with 17beta-estradiol (EST, 10 microg x kg(-1) x day(-1)), and GEN (5 mg x kg(-1) x day(-1)). At 15 weeks postoperation, the compressive test was performed on the L5 vertebral body; additionally, microcomputed tomography (micro-CT) assessment was performed to estimate the bone mineral density (BMD) and microstructure parameters of the L6 vertebral body. After fatigue damage testing, the L6 vertebral body was bulk-stained in 1% basic fuchsin and embedded in methylmethacrylate. The L4 vertebral body was embedded in methylmethacrylate for dynamic histomorphometry analysis without staining. Mounted bone slices were used to measure microcrack parameters, empty osteocyte lacuna density (e.Lc.Dn), and osteocyte density (Ot.N/T.Ar). Maximum loading (ML) and Ot.N/T.Ar were significantly lower in the OVX group than in the other groups. E.Lc.Dn was significantly decreased in GEN and EST groups compared to the OVX group. ML was significantly decreased in the GEN group compared to the SHAM group. Microcrack density, microcrack surface density, and microcrack length were significantly increased in the OVX group compared to the other groups. Mineral apposition rate was significantly decreased in the OVX group compared to the SHAM and GEN groups. Bone formation rate was significantly decreased in the OVX group compared to other groups. There were no significant differences with regard to mineralizing surface among the four groups. Volumetric BMD at organ was significantly lower in OVX, EST, and GEN groups than in the SHAM group. Bone mineral content was significantly lower in the OVX group than in the SHAM group. Bone volume fraction and trabecular number were significantly decreased in OVX, EST, and GEN groups compared to the SHAM group. Structure model index was significantly lower in the SHAM group than in OVX, EST, and GEN groups. Trabecular separation was significantly increased in the OVX group compared to SHAM and EST groups. There were no significant differences with regard to the trabecular thickness (Tb,Th) between SHAM, GEN, and OVX groups. Tb.Th was significantly lower in the EST group than in the SHAM group. Connectivity density (Conn.D) was significantly lower in the OVX group than in SHAM and GEN groups, and Conn. D was significantly lower in the EST group than in GEN. In conclusion, the present study demonstrates that GEN preserved the biomechanical quality of the trabecular bone regardless of the microstructure and BMD.     

50 Hz 1.8 mT正弦交变电磁场通过促进骨形成抑制尾吊大鼠的骨量丢失

目的探究50 Hz 1.8 m T正弦交变电磁(sinusoidal electromagnetic fields,SEMFs)是否能抑制尾吊(hind-limb suspension,HLS)所致大鼠的骨量丢失。方法 30只雌性SD大鼠(180±10)g,分为3组,每组10只,分别为对照组、HLS组和HLS+SEMFs组。除对照组外,HLS组和HLS+SEMFs组大鼠进行尾吊,之后,HLS+SEMFs组大鼠每天进行1.5 h 50 Hz1.8 m T正弦交变电磁场干涉。4 w后处死全部大鼠,对各组大鼠进行重要脏器的器官指数计算和病理学观察、离体骨密度检测、骨生物力学分析和骨形态计量学分析以及Micro-CT扫描。结果实验期间各组大鼠的体重及重要脏器的器官指数差异无统计学意义(P0.05),脏器病理学观察未见异常变化;骨密度结果显示,SEMFs有效提高股骨和椎骨的离体骨密度;生物力学实验表明,SEMFs减轻了HLS引起的股骨和椎骨力学性能的降低。此外,SEMFs能增加骨钙素(osteocalcin,OC)含量,并且对抗酒石酸酸性磷酸酶5b(tartrate-resistant acid phosphatase 5b,TRACP-5b)具有一定的抑制作用;Micro-CT结果显示,SEMFs部分抑制HLS造成的松质骨骨微结构的减少,相比HLS组,骨小梁数、骨小梁厚度、骨小梁面积显著升高,且分离度下降;骨组织形态学分析同样表明SEMFs改善了松质骨骨微结构的恶化。结论 50 Hz 1.8 m T SEMFs能抑制HLS所致大鼠的骨量丢失,其可能机制是具有抑制骨吸收和提高骨形成的双重活性,这将为电磁场治疗骨质疏松症的临床应用提供依据。     

The effects of nandrolone decanoate on bone mass and metabolism in ovariectomized rats with osteopenia

The effects of nandrolone decanoate (ND) treatment on bone mass and metabolism were studied in ovariectomized (OVX) rats with osteopenia. The 6-month-old rats were divided into Sham (n = 12) and OVX (n = 24). The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post ovariectomy, the OVX rats were divided into two groups: (1) OVX + Vehicle and (2) OVX + ND. The effects of ND on bone mineral density (BMD), bone mineral content (BMC), and bone metabolism were studied by dual-energy X-ray absorptiometry (DXA) and biochemical markers including urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr), and serum osteocalcin. After 24 weeks of treatment, histomorphometry of the right tibiae and the wet weight of the gastrocnemius and soleus skeletal muscles were also examined. Ovariectomy resulted in a significant increase in biochemical markers and a significant decrease in spine BMD (0.221 ± 0.016 g/cm² in OVX group vs 0.239 ± 0.008 g/cm² in Sham group) and BMC (0.550 ± 0.055 g in OVX group vs 0.605 ± 0.042 g in Sham group) at 6 weeks post ovariectomy. Spine BMD (0.227 ± 0.017 g/cm²), femoral BMD (0.263 ± 0.012 g/cm²), and bone density of femur (1.035 ± 0.036 g/cm³) in the OVX + ND group were significantly greater than those in the OVX + Vehicle group (0.204 ± 0.013 g/cm² for spine BMD, 0.243 ± 0.009 g/cm² for femoral BMD, 0.938 ± 0.06 g/cm³ for bone density of femur) after 24 weeks of treatment. ND treatment decreased urinary Pyr and Dpyr significantly in OVX rats. Histomorphometric findings indicated that ND-treated rats had greater cancellous bone volume, greater trabecular number, greater trabecular thickness, and less trabecular separation than vehicle-treated OVX rats. OVX rats had greater wet weight of the gastrocnemius and soleus muscles than rats treated with ND. The data suggest that the effect of ND on bone mass is not influenced by the condition of the muscles in OVX rats. Our findings indicate that ND blocks further bone loss by inhibition of bone resorption in OVX rats with osteopenia. Received: August 25, 1999 / Accepted: January 28, 2000     

The Phytoestrogen Genistein Reduces Bone Loss in Short-Term Ovariectomized Rats

The incidence of fractures and of osteoporosis differs between Oriental and Western Caucasian women. This may depend, at least in part, on nutritional factors, including dissimilarities in dietary intake of phytoestrogens. To investigate this possibility, 2-month-old female rats were ovariectomized (OVX) or sham-operated (SHAM), fed a casein-based diet, injected daily with subcutaneous genistein (GEN), the most abundant and best characterized phytoestrogen, or vehicle (Veh) and killed 21 days after surgery. As expected, ovariectomy resulted in loss of bone mineral density (BMD) and in uterine atrophy. However, administration of 5 mg GEN per gram body weight (b.w.) ameliorated the ovariectomy-induced loss of BMD (189 ± 2 mg/cm² in OVX and 192 ± 2 in OVX with 5 mg GEN/g b.w. per day; p<0.05). One microgram GEN per gram body weight did not affect the BMD loss and the effect of the 5 mg and 25 mg GEN per gram body weight were statistically not different. A trend toward reduced uterine atrophy (21% reduction) was noted with the 25 mg GEN dose, but not with the 1 mg and 5 mg doses. A separate experiment with 2 x 2 factorial design was conducted to elucidate the mechanism by which GEN ameliorates ovariectomy-induced bone loss. In this experiment, histomorphometry demonstrated a dramatic reduction in trabecular bone volume after ovariectomy (7.6 ± 0.7% of total bone volume in SHAM-Veh vs 3.3 ± 0.2% in OVX-Veh; p<0.01) and less bone loss in OVX rats injected with 5 mg GEN per gram per day (3.3 ± 0.2% of total bone volume in OVX-Veh vs 5.2 ± 0.4% in OVX-GEN; p<0.01). Administration of GEN was associated with higher bone formation rate per tissue volume and with a trend toward a higher number of osteoblasts per bone perimeter. The parameters of bone resorption were not affected by GEN. The concentration of serum osteocalcin and the urinary excretion of deoxypyridinoline provided corroborating results. Since production of proinflammatory cytokines is intimately involved in the pathogenesis of postmenopausal osteoporosis, the effect of GEN on lipopolysaccharide-induced in vitro production of Tumor necrosis factor-alpha (TNFa) was tested in monocytic cells from the same four rat groups. Production of TNFa was markedly elevated in OVX-Veh as compared with the SHAM-Veh rats, but this was blocked by GEN in the OVX rats. This study shows that GEN reduces both trabecular and compact bone loss after ovariectomy and that this protective effect differs from that of estrogen, since it depends on stimulation of bone formation rather than on suppression of bone resorption. Lack of action of GEN on uterine atrophy supports the possibility that this GEN dose affects target tissues via non-estrogenic mechanisms. Modulation of cytokine production may be involved in the effect of GEN on bone. Received: 27 June 1997 / Accepted: 27 October 1997     

悬吊模拟失重及解悬吊对大鼠骨密度及生物力学的影响

目的：观察尾部悬吊模拟失重及解悬吊后大鼠骨密度及生物力学的变化。方法：20只Wistar雄性大鼠随机分成空白组和模型组。模型组尾部悬吊14d,解悬吊后继续饲养14d,空白组则正常饲养28d。实验第14天活体检测各组大鼠颅骨、T2椎体、L4椎体、骨盆、右侧桡尺骨和右侧股骨的骨密度（bone mineral density,BMD）;实验第28天处死大鼠,检测右侧股骨及L4椎体BMD及生物力学强度。结果：与空白组相比,实验第14天,模型组大鼠股骨、骨盆、腰椎BMD明显低,差异有统计学意义（P〈0.001,P〈0.001,P〈0.01）;颅骨、胸椎、桡尺骨BMD无明显变化（P〉0.05）。实验第28天,模型组大鼠股骨、腰椎BMD和股骨最大载荷明显低,差异有统计学意义（P〈0.01,P〈0.001,P〈0.01）。结论：大鼠尾部悬吊14d即可引起骨代谢的紊乱：承重骨骨矿盐大量丢失;即使解悬吊14d后承重骨BMD及力学强度也明显降低,表明骨代谢紊乱短期内不能恢复正常。     

How many days per week should rats undergo running exercise to increase BMD?

The aim of the present study was to examine the effect of different frequencies of running exercise on increasing bone mineral density (BMD) and improving bone histomorphology at various sites of the skeleton (tibia, femur, and second lumbar vertebra) in young rats. Twenty-five female Wistar rats, 8 weeks old, were divided into five groups, of 5 animals each according to running load: control group, no running (A group); running load (RL), 4 days per week (d/w; B group); RL, 5 d/w (C group); RL, 6 d/w (D group); and RL, 7 d/w (E group). Rats ran on a treadmill at a speed of 15 m/min for 30 min per day over an 8-week period. The results indicated that the BMD of the tibia in the B, C, D, and E groups and that of the femur in the B and E groups increased significantly over that of the A group. However, the cortical BMD and trabecular BMD of the second lumbar vertebra did not change. In regard to bone histomorphometry of the tibia, a parameter of bone resorption (eroded surface/bone surface) was significantly lower in the B and D groups than in the A group. There were no differences in the parameters of bone formation. Tartaric acid-resistant acid phosphatase (TRACP) values were significantly lower in the B and C groups than in the A group. There were significant increases in body weight in the B group and in muscle weight in the C group. From the data obtained in this study, it was concluded that increases in BMD were obtained by a moderate running load at frequencies of 4 and 5 days per week.