去卵巢大鼠骨髓微环境中RUNX2\PPARγ基因及OPG\RANKL基因蛋白表达变化的实验研究

[目的]探讨在去卵巢大鼠骨质疏松模型骨髓微环境中成骨细胞、脂肪细胞和破骨细胞分化的相互关系及其机制.[方法]将3个月龄雌性SD大鼠16只随机分为2组:假手术组(SHAM)和去卵巢组(OVX),每组8只.采用双侧卵巢切除术复制骨质疏松大鼠模型.术后14周,应用双能X线吸收仪法(DXA)测第4腰椎和股骨骨密度(BMD).qRT-PCR法测量骨髓细胞RUNX2、PPARγ、OPG和RANKL mRNA表达量.石蜡组织切片HE染色测量第3腰椎和胫骨近端骨组织脂肪细胞数目.免疫组织化学染色测定胫骨近端骨组织OPG/RANKL蛋白表达量.[结果]与SHAM比较,OVX组腰椎和股骨BMD下降(P＜0.05).OVX组股骨骨髓细胞成骨分化转录因子RUNX2 mRNA水平比SHAM组增高(P＜0.05),成脂分化转录因子PPAR γ mRNA表达水平比SHAM组增高(P＜0.05).OVX组胫骨和第3腰椎脂肪细胞数目比SHMA组增多(P＜0.05).与SHAM组比较,OVX组股骨骨髓细胞RANKLmRNA和胫骨RANKL蛋白表达量增加(P＜0.05)且OPG/RANKL的比率都降低(P＜0.05),而两者OPG的mR-NA和蛋白表达量无统计学差异(P＞0.05).[结论]去卵巢大鼠骨量丢失可能是骨髓微环境中成骨细胞分化、脂肪细胞分化和破骨细胞分化紊乱导致.     

去卵巢对大鼠骨密度的影响

目的：探讨去卵巢对大鼠骨密度（BMD）的影响。方法；20只3．5月龄SD雌性大鼠分别除双侧卵巢（OVX）或假性去卵巢（Sham)，术后14周处死，应用QDR－4500A型扇形束双能X射线吸收法（DXA）测量大鼠全身、离体股骨、胫骨、腰维及兴趣区的BMD。结果：①术后6周OVX组全身BMD显低Sham组（P＝0．048），术后14周两组无显性差异；②术后14周OVX组离体股骨BMD显低于Sham组（P＜0．01），股骨远侧干骺端平均降低11．6％（P＜0．001）；③术后14周右侧离体胫骨BMD两组间差异无显性，但OVX组胫骨的端干骺端BMD显低于Sham组（P＜0．001）；④术后14周OVX组腰椎（L4－L6）的BMD显低于Sham组（P＝0．014），第六腰椎降低明显，平均降低8．1％（P＝0．005）。结论：去卵巢所致骨丢失以松质骨含量丰富的兴趣区明显。     

基于OPG/RANKL/RANK轴观察加味阳和汤及其拆方对去卵巢骨质疏松大鼠的影响

目的观察加味阳和汤及其拆方对OPG、RANKL、RANK含量的影响,探讨其防治绝经后骨质疏松症可能的作用机制及组方配伍的合理性。方法选取48只雌性SD大鼠,加味阳和汤按君臣佐使关系拆方,将大鼠等量随机分为假手术组(SHAM)、模型组(OVX)、君药+臣药组(A组)、君药+臣药+佐药组(B组)、君药+臣药+佐药+使药组(C组)、戊酸雌二醇组(E2V)。除SHAM组外,均采用去卵巢骨质疏松大鼠模型,干预给药后(灌胃90 d),处死动物后取右侧股骨及胫骨通过双能X射线骨密度仪检测骨密度(bone mineral density,BMD)及骨矿含量(bone mineral content,BMC),取左侧股骨行HE染色观察骨显微结构,检测血清中骨代谢指标ALP、Ca~(2+)、P~(3-)、E2及血清OPG、RANKL、RANK含量。结果与SHAM组相比,OVX组大鼠股骨及胫骨BMD、BMC降低(P0.05),骨小梁变细、间隙增大、结构缺失,血清Ca~(2+)、P~(3-)、E2、OPG水平下降(P0.05),血清ALP、RANKL、RANK水平上升(P0.05);与OVX组比较,除A组大鼠股骨及胫骨BMD、BMC、血清Ca~(2+)、P~(3-)、E2、OPG、RANKL及B组P~(3-)水平无显著差异外(P0.05),各给药组大鼠股骨及胫骨BMD、BMC均显著升高(P0.05),骨小梁增多、间隙减小、结构趋向完整,血清Ca~(2+)、P~(3-)、E2、OPG水平上升(P0.05),血清ALP、RANKL、RANK水平下降(P0.05)。结论加味阳和汤及其拆方通过提高去卵巢骨质疏松大鼠BMD、BMC,降低骨代谢,改善骨显微结构从而发挥治疗作用,调节OPG/RANKL/RANK轴是可能的机制。     

仙灵骨葆对卵巢切除小鼠骨质疏松症的影响

目的 利用卵巢切除骨质疏松症小鼠模型,研究仙灵骨葆抗骨质疏松症的疗效.方法 30只129SV品系雌性小鼠随机分为三组:卵巢假切+安慰剂组(SHAM+NS,0.2 ml·d-1);卵巢切除+安慰剂组(OVX+NS,0.2 ml·d-1),卵巢切除+仙灵骨葆组(OVX+XLGB,500 mg·kg-1·d-1),持续治疗12周后取材,应用Micro-CT检测骨密度(BMD)和骨小梁结构、组织病理切片观察骨形态、三点弯曲试验和压缩试验检测骨生物力学指标.结果 Micro-CT 检测股骨BMD,OVX+NS组BMD(498.6±13.0 mg/cm2)较SHAM+NS组(636.5±12.4 mg/cm2)下降22%(P＜0.01),OVX+XLGB组BMD (561.0±18.6 mg/cm2) 与OVX+NS组相比提高了13%(P＜0.05).Micro-CT检测小鼠腰椎(L2-5)骨小梁结构显示:OVX+NS组骨小梁BV/TV、Tb.Th 分别低于SHAM+NS组22%、35%,Tb.Sp高于SHAM+NS组11%,差异有统计学意义(P＜0.05).给予仙灵骨葆治疗后,腰椎BV/TV及Tb.Th分别高于OVX+NS组15%、16%,Tb.Sp低于OVX+NS组9%,具有显著性差异(P＜0.05).三点弯曲和压缩试验检测OVX+NS组股骨和腰椎的最大载荷和最大应力,股骨最大载荷和最大应力较SHAM+NS组显著降低42%、49%,腰椎最大载荷和最大应力显著降低42%、43%(P＜0.05).仙灵骨葆治疗后,股骨和腰椎的最大载荷分别提高了75%和47%,最大应力分别提高了47%和47%,差异有统计学意义(P＜0.05).结论 仙灵骨葆能够显著提高卵巢切除引起的骨密度,改善骨微结构破坏,提高骨生物力学参数,表明仙灵骨葆具有良好的抗骨质疏松症疗效.     

MicroPET/CT评价去卵巢大鼠骨代谢变化的实验研究

目的探讨使用microPET/CT扫描仪对骨质疏松非创伤性探查的可行性,分析去卵巢大鼠雌激素缺乏引起骨质疏松的骨代谢变化。方法 12只6月龄雌性未孕Sprague-Dawley大鼠,体重290 g～310 g,随机分为两组(n=6):去卵巢组(OVX)和假手术组(SHAM)。用microPET/CT扫描仪进行骨显像,检测大鼠第4腰椎椎体、左股骨近端,左股骨干以及左胫骨中段对核素显像剂18F-F-的摄取。骨显像检测后腹主动脉放血法处死大鼠,取子宫称重,收集第4腰椎、左侧股骨和胫骨,用双能X线骨密度检测仪(DXA)测定第4腰椎椎体、左股骨近端,左股骨干以及左胫骨干的骨密度,取大鼠右侧胫骨制备成不脱钙硬组织切片进行形态学观察。结果 OVX组第4腰椎椎体、左股骨近端,左股骨干以及左胫骨干的骨密度比SHAM组有显著性下降。与SHAM组比较,microPET/CT骨显像可见OVX组第4腰椎椎体、左股骨近端,左股骨干以及左胫骨干核素浓聚,去卵巢大鼠骨骼兴趣区PET影像强度增加。两组大鼠胫骨干的骨几何结构参数比较无显著性差异,OVX组大鼠胫骨近端松质骨的结构参数与SHAM组比较有明显变化。OVX组大鼠胫骨近端的骨形成参数矿化表面、矿物质沉积率和骨形成率比SHAM组有显著性升高。两组大鼠胫骨第4腰椎椎体、左股骨近端,左股骨干以及左胫骨干PET影像强度与其骨密度之间呈显著性负相关。结论 MicroPET/CT可用于骨质疏松大鼠的骨代谢研究,为临床诊断骨质疏松新方法研究提供了新思路。     

雌激素治疗去卵巢大鼠骨丢失的不同部位效应观察

目的探讨雌激素对去卵巢(OVX)大鼠骨丢失的作用敏感部位。方法8月龄SD大鼠去卵巢后,皮下注射17β-雌二醇(E2)(10、30μg.kg-1.d-1)3月,双能X线骨密度仪检测全身总骨密度(BMD),离体腰椎(L4-6)、股骨、胫骨BMD。实验分为假手术组、去卵巢模型组、雌激素小剂量组、雌激素大剂量组,每组10只。结果E2可逆转OVX所致总BMD降低,增加OVX后腰椎整体及3个兴趣区BMD。E2治疗可升高OVX后股骨BMD,其中股骨整体、股骨近端和股骨远端处改变最为明显(P<0.01),其余各兴趣区BMD改变相对稍弱,而股骨中段最不敏感。胫骨BMD指标中以胫骨近端最为敏感(P<0.01),而中远端几乎无改变。结论雌激素对去卵巢(OVX)大鼠的作用敏感部位与骨量丢失敏感部位具有一致性,雌激素增加骨密度主要在腰椎、股骨近端、股骨远端和胫骨近端。     

鲑鱼降钙素对去卵巢大鼠骨髓细胞OPG、RANKL基因和蛋白表达的影响

[目的]观察鲑鱼降钙素(sCT)对去卵巢大鼠骨密度(BMD)、血清Ⅰ型胶原交联羧基末端肽(ICTP)变化的影响,以及骨髓细胞骨保护素(OPG)和核因子κB受体活化因子配体(RANKL)的基因表达和两者在胫骨骨骺端蛋白含量的变化.[方法]取3个月龄雌性SD大鼠24只,随机平均分3组:假手术组(Sham)、鲑鱼降钙素处理组(sCT)、安慰剂组(OVX).采用双侧卵巢切除术复制骨质疏松大鼠模型.术后2周CT组予鲑鱼降钙素皮下注射12周,应用双能X线吸收仪法(DXA)测BMD,ELISA法测量血清ICTP浓度,qRT-PCR法定量骨髓细胞OPG和RANKL的mRNA表达量,免疫组织化学染色法测定胫骨干骺端OPG和RANKL蛋白表达量.[结果]与OVX组比较,sCT组的腰椎BMD上升显著(P＜0.05),但股骨BMD改变不明显(P＞0.05);血清ICTP含量显著降低(P＜0.05);骨髓细胞RANKL的mRNA表达量变化不大(P＞0.05),但OPG的mRNA表达量升高(P＜0.05),OPG/RANKL的比率升高(P＜0.05);胫骨干骺端也呈现出RANKL蛋白改变不明显(P＞0.05),而OPG的蛋白分泌增加(P＜0.05),从而OPG/RANKL的比率高于OVX组(P＜0.05)的现象.[结论]降钙素可以预防腰椎BMD的丢失,降低血清ICTP水平,在体内可能主要通过上调OPG的mRNA表达和蛋白分泌,影响OPG/RANKL/RANK系统,影响破骨细胞功能,抑制骨吸收,进而达到预防绝经后骨质疏松的目的.     

糖皮质激素干预后大鼠骨量、骨转换指标、雌激素水平变化及其相互关系

目的探讨糖皮质激素(glucocorticoid,GC)干预后不同时间点大鼠骨量、骨转换指标、雌激素水平的变化及其相互关系。方法取3月龄雌性SD大鼠34只,体质量(208.73±23.94)g,随机分为基线组(n=6)、对照组(n=14)、地塞米松(dexamethasone,DXM)组(n=14)。DXM组皮下注射DXM 0.75 mg/kg,每周2次,连续12周;对照组注射等量生理盐水;基线组大鼠不做处理。基线组于实验前,对照组及DXM组于4、8、12周取大鼠,测量体质量及子宫、肾上腺重量;ELISA法测量血清中Ⅰ型前胶原氨基末端前肽(N-terminal propeptide of type I procollagen,PINP)、Ⅰ型胶原羧基端肽(C-terminal cross-linking telopeptide of type I collagen,β-CTX)及雌激素水平;采用双能X线骨密度仪扫描L1~3椎体及左侧股骨,测量股骨头颈、股骨粗隆、股骨干、股骨全段和L1、L2、L3、L1~3区域的骨密度(bone mineral density,BMD)、骨矿物含量(bone mineral content,BMC)、骨面积(bone area,BA)。对大鼠的体质量、腰椎BMD、股骨BMD、PINP、β-CTX、雌激素水平进行相关性分析。结果各时间点DXM组大鼠体质量及子宫、肾上腺重量均显著低于对照组及基线组(P0.05)。DXM组激素干预后大鼠血清PINP、β-CTX升高,但4、8周时与基线组及对照组比较差异无统计学意义(P0.05),12周时差异有统计学意义(P0.05);大鼠血清雌激素水平下降,各时间点均较基线组及对照组明显降低(P0.05)。各时间点DXM组BMD、BMC、BA均显著低于对照组(P0.05),其中以L2及股骨粗隆部骨量丢失最严重。4周时,L1 BMC、BA及股骨干BA较基线组显著降低(P0.05),而其余部位BMD、BMC、BA在各时间点与基线组比较,差异均无统计学意义(P0.05)。相关分析显示,腰椎及股骨BMD与PINP、β-CTX成负相关(P0.05),与雌激素水平成正相关(P0.05)。结论 GC干预后大鼠腰椎及股骨骨量呈先快速降低、再维持低水平趋势,骨转换指标在激素干预后呈持续上升趋势,血清雌激素水平呈整体下降趋势,体质量、骨转换指标及雌激素水平与骨量密切相关。     

间歇皮下注射人甲状旁腺激素不同片段(hFTH1-34及 hFTH1-84)对去卵巢大鼠股骨及腰椎骨量的影响

目的 比较间歇皮下注射人甲状旁腺激素不同片段（hPTH1-34)及（hPTH1-84)对完整雌性（Non-OVX)大鼠和去卵巢（OVX）大鼠股骨及腰椎1－4骨矿物含量（BMC）和骨密度（BMD）的影响。方法 Wistar雌性大鼠176只，分为hPTH1-34和hPTH1-84两大组（各80只及96只），每大组及各自分4组（每组各20只或24只），分别为：两组安慰剂组（未切卵巢及切卵巢）用安慰剂（PBS）进行皮下注射，每周3次，共2周；两组治疗组（未切卵巢及切卵巢）用hPTH1-34或hPTH1-84，皮下注射，每周3次，共2周。结果 1．卵巢切除术后3个月大鼠股骨及腰椎1－4BMC和BMD明显下降；2．两种片段的甲状旁腺激素（hPTH1-34及pPTH1-84)间歇注射均能使Non-OVX大鼠和OVX大鼠股骨及腰椎1－4BMC和BMD较相应对照组明显升高；且腰椎1－4较股骨的BMC和BMD升高更明显；3．OVX大鼠治疗后股骨与腰椎1－4BMC和BMD的升高率较Non-OVX大鼠更明显；OVX大鼠在治疗后股骨及腰椎骨量能恢复到去卵巢前水平；4．hPTH1-34较hPTH1-84更明显的使完整大鼠和OVX大鼠股骨BMC和BMD升高。结论 间歇皮下注射人甲状旁腺激素对大鼠股骨及腰椎骨量均有增高作用，尤其对腰椎的骨量以及对去卵巢大鼠骨量升高作用更明显；hPTH1-34片段对大鼠股骨骨量的增高作用强于hPTH1-84片段。     

选择性雌激素受体调节剂-雷诺昔酚对去势后大鼠骨组织中TNF-α表达的影响

目的 了解选择性雌激素受体调节剂（SERM）对去卵巢大鼠骨组织形态计量学指标、骨密度及松质骨中TNF-α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（SHAM）组、去势（OVX）组、去势＋雷诺昔酚（OVX＋RAL）组.OVX＋RAL组大鼠术后第2天开始给予雷诺昔酚灌胃.术后20 wk处死各组大鼠,对各组大鼠不同部位骨组织形态计量学指标、骨密度（BMD）进行检测,并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TNF-α表达图像进行分析,观察RAL对OVX大鼠腰椎松质骨中TNF-α表达的影响.结果 （1）与SHAM组相比,OVX组大鼠骨小梁体积、骨小梁平均厚度、皮质骨厚度等骨形态计量学指标明显下降（P＜0.01）,OVX＋RAL组大鼠骨形态计量学指标明显大于OVX组（P＜0.01）,接近SHAM组水平（P＞0.05）;（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）;RAL治疗组各部位BMD高于OVX组（P＜0.01或P＜0.05）,接近SHAM组水平（P＞0.05）;（3）去势组与SHAM组相比较,TNF-α表达的灰度值明显降低（P＜0.01）;RAL组较OVX组灰度值明显升高（P＜0.01）,经RAL治疗后的去卵巢大鼠骨小梁周围及髓腔内TNF-α阳性表达明显减弱（P＜0.01）,接近SHAM组水平（P＞0.05）;结论 RAL可通过抑制破骨性因子TNF-α表达来抑制因雌激素缺乏引起的骨密度降低及骨形态结构退变.     

中等强度跑台运动对去卵巢大鼠后肢骨骨矿物含量和骨密度的双重调节作用

目的 观察中等强度跑台运动对去卵巢大鼠后肢骨骨矿物含量(BMC)和骨密度(BMD)的影响.方法 将60只3月龄未经产雌性SD大鼠按体重随机分为假手术、去卵巢静止、去卵巢运动Ⅰ、去卵巢运动Ⅱ、去卵巢运动Ⅲ和去卵巢运动Ⅳ 6个组.各运动组经1周的跑台适应训练后,按实验设计分别进行为期14周的正式跑台训练.实验结束时,腹主动脉取血处死大鼠,双能χ-射线骨密度仪检测右侧游离股骨和胫骨的BMC和BMD.结果 ①与假手术组相比,去卵巢静止组股骨近端和远端以及胫骨近端BMC和BMD显著下降,但股骨中段以及胫骨中段和远端BMC和BMD无显著变化.②与去卵巢静止组相比,去卵巢运动Ⅰ组股骨近端和远端BMC显著增加,股骨中段以及胫骨3个部位BMC均无显著变化;去卵巢运动Ⅱ组和Ⅲ组股骨和胫骨3个部位BMC 均无显著变化;去卵巢运动Ⅳ组股骨3个部位BMC均无显著变化,而胫骨3个部位BMC均显著下降.③与去卵巢静止组相比,去卵巢运动Ⅰ组股骨近端和远端以及胫骨近端BMD 显著增加, 而股骨中段和胫骨中段和远端BMD无显著变化;去卵巢运动Ⅱ组和Ⅲ组股骨和胫骨任何部位BMD均没有显著变化;去卵巢运动Ⅳ组股骨3个部位BMD无显著变化,而胫骨3个部位BMD却显著下降.结论 较低中等强度跑台运动能减缓去卵巢大鼠股骨近端和远端骨矿物含量和骨密度的下降;而较高中等强度跑台运动却能加速去卵巢大鼠胫骨近端骨矿物含量和骨密度的下降.     

Differences in Bone Turnover and Skeletal Response to Thyroid Hormone Treatment Between Estrogen-Depleted and Repleted Rats

This study was undertaken to compare the effect of supraphysiological doses of thyroxine (T4) on bone metabolism in SHAM and OVX young adult rats. Female Sprague Dawley rats (220 ± 2 g, approx. 5 months of age) were divided into four groups of eight animals each. The animals were intraperitoneally injected 6 days per week with vehicle (Vh): 0.001 N NaOH/0.9% NaCl (SHAM+Vh and OVX+Vh) or 250 μg of thyroxine/kg/day (SHAM+T4 and OVX+T4) during a 5-week period. Serum T4 and osteocalcin (BGP), urinary pyridinolines (Pyr), and creatinine (creat) were determined. At the beginning and at end of the experiment, skeletal bone mineral content (BMC), bone mineral density (BMD), and area (A) of the total skeleton, femur, spine, and whole tibia, as well as proximal, middle, and distal areas of the tibia were assessed by dual X-ray absorptiometry (DXA) in an ultra-high-resolution mode. T4 treatment of the SHAM rats did not induce significant changes in BGP level or Pyr/creat excretion compared with the SHAM+Vh control group. However, these two biochemical bone markers significantly increased due to T4 treatment in OVX rats compared with both OVX+Vh and SHAM+T4 groups (P < 0.05 and P < 0.001, respectively). The OVX+T4 group had a significantly lower ΔBMD than SHAM+T4 rats in all studied regions (P < 0.05) except for the middle tibia region. OVX+T4 groups presented a significantly lower ΔBMC and ΔA compared with SHAM+T4 animals (P < 0.001). OVX+T4 rats significantly impaired the ΔBMD in the femur (P < 0.01), spine (P < 0.05), whole (P < 0.05) and middle (P < 0.05) tibia whereas T4 treatment of SHAM rats only affected, significantly, the whole (P < 0.05) and the proximal tibia region (P < 0.01). T4 treatment affects bone growth in young adult rats. The effect is significantly greater in the estrogen-depleted than in the estrogen-repleted state. The bone site most adversely affected by T4 treatment depends on the estrogen status. The proximal tibia (principally trabecular bone) was the most affected area in estrogen-repleted rats. Conversely, in OVX rats, the middle tibia (principally cortical bone) presented the greatest decrease in bone density. Received: 20 May 1999 / Accepted: 4 February 2000     

Reductions in bone mass, structure, and strength in axial and appendicular skeletons associated with increased turnover after ovariectomy in mature cynomolgus monkeys and preventive effects of clodronate.

Over 16 months, we evaluated the effects of ovariectomy (OVX) and bisphosphonate clodronate (CLO) on bone in 48 cynomolgus monkeys (9-15 years old) fed a normal calcium diet. We established three OVX groups (oral CLO at 0 [OVX control], 12, or 60 mg/kg per day) and one sham-operated (SHAM) group. At 16 months, the bone mineral density (BMD) values (percentage of group baseline; OVX control vs. SHAM) for lumbar bone (L3-L5), proximal femur, midfemur, radius, and tibia were -2.6% versus 11.2%, -3.5% versus 8.9%, -3.0% versus 9.0%, -5.5% versus 15.7%, and -6.7% versus 13.9%, respectively. In OVX control (i) tibia showed significant loss of bone mineral content (BMC; vs. baseline), (ii) urinary deoxypyridinoline (DPD) and serum osteocalcin (OC) levels increased (peak = 182% and 168%, respectively, of SHAM), (iii) in lumbar bone and midfemur, ultimate load (UL) was reduced (vs. SHAM), (iv) in lumbar bone, trabecular bone-formation rates (BFRs) were not changed significantly, but tibial endocortical and intracortical bone formation rates were significantly raised (vs. SHAM), (v) the volumetric BMD (vBMD) and geometry of the tibial cortex (measured by peripheral quantitative computed tomography [pQCT]) were significantly reduced (vs. SHAM). CLO, 60 mg/kg per day but not 12 mg/kg per day, significantly inhibited OVX-induced changes, age-dependent increases in bone mass, and ability to maintain structure. Thus, in OVX mature cynomolgus monkeys (possibly, a unique model of the cortical bone loss secondary to estrogen deficiency), the post-OVX increases in systemic bone markers were slight, but stimulation of local turnover in the cortical envelope was enough to cause bone loss (more so in tibia than in lumbar trabecular bone). High-dose CLO prevented these changes.     

鹿瓜多肽注射液对去势大鼠骨密度和骨力学性能的影响

目的研究鹿瓜多肽注射液对去卵巢大鼠骨骼生物力学性能的影响。方法 3个月龄清洁级雌性Wistar大鼠27只,随机分为假手术（sham group,SHAM）组、去势（ovariectomized,OVX）组、去势＋鹿瓜多肽（cervus and cu-cumis polypeptide,CCP）组,每组9只。OVX＋CCP组大鼠于术后第1天开始按0.6 mL/（kg.d）肌注鹿瓜多肽注射液,术后12周处死所有大鼠,取出股骨及腰椎标本,双能X线吸收仪测量各组大鼠股骨近端、股骨干及全腰椎的骨密度。应用INSTRON 3367电子拉伸试验机检测股骨近端、股骨干和L5的生物力学性能。结果 a）OVX组与SHAM组相比较,大鼠股骨和腰椎最大载荷无明显下降（P〉0.05）,但极限强度明显下降（P〈0.01）;与OVX组相比,OVX＋CCP组的最大载荷无明显增加（P〉0.05）,但极限强度显著高于去势组（P〈0.01）;OVX＋CCP组与SHAM组比,上述检测指标间无统计学差异（P〉0.05）;b）与SHAM组相比,OVX组股骨近端、股骨干及全腰椎的骨密度明显降低（P〈0.01）;与OVX组相比,OVX＋CCP组各部位骨密度明显高于OVX组（P〈0.01）;OVX＋CCP组与SHAM组比,两者各部位骨密度无明显差异（P〉0.05）。结论鹿瓜多肽注射液能保护去势大鼠骨密度和骨骼内在生物力学性能。     

Do Different Aminobisphosphonates Have Similar Preventive Effect on Experimental Thyroid Hormone-Induced Osteopenia in Rats?

We compared similar doses of three different aminobisphosphonates (BP): olpadronate (OPD), pamidronate (APD), and alendronate (ALE) on osteopenia induced by thyroxine (T4)-treatment in OVX and SHAM adult rats. Female Sprague Dawley rats (259 +/- 8 g) were treated with vehicle (SHAM+Vh and OVX+Vh), 250 microg T4/kg/day (SHAM+T4 and OVX+T4), 0.3 mg OPD/kg/day (SHAM+OPD and OVX+OPD), 0.2 mg ALE/kg/day (SHAM+ALE and OVX+ALE), 1.5 mg APD/kg/day (SHAM+APD and OVX+APD), T4+OPD (SHAM+T4+OPD and OVX+T4+OPD), T4+ALE (SHAM+T4+ALE and OVX+T4+ALE), and T4 +APD (SHAM+T4+APD and OVX+T4+APD) during a 5-week period. At the onset and at the end of the experiment, total skeleton bone mineral density (BMD) was assessed in vivo by DXA. Lumbar spine and proximal tibia BMDs were evaluated. T4 treatment to SHAM rats did not modify BGP levels significantly: neither did ovariectomy. T4 treatment to OVX rats significantly increased bone-gla-protein (BGP) levels compared with the other studied groups (P < 0.05). BP treatment reduced BGP levels to values significantly lower than SHAM rats (P < 0.05) and reduced bone alkaline phosphatase in SHAM groups (P < 0.05) but no changes were found in OVX groups. The increased D-Pyr excretion observed in SHAM+T4 rats (P = 0.056), OVX+Vh (P < 0.05), and OVX+T4 group (P < 0.001) compared with the SHAM+Vh rats was prevented by the BP treatment. OVX+Vh rats had total skeleton and proximal tibia BMD, and OVX+T4 group had total skeleton, spine, and proximal tibia BMD significantly lower than the SHAM+Vh group. BP treatment was also found to prevent this reduction. The reduced bone resorption and the prevention of bone loss showed no differences among very close, potentially equivalent doses of the three aminoBPs used. Consequently, treatment with very close similar doses of APD, ODP, and ALE prevented bone resorption and bone changes with the same efficacy.     

应用pQCT与DXA定量检测去卵巢大鼠股骨近端骨质疏松建模效果的对比研究

目的比较pQCT与DXA定量检测去卵巢大鼠股骨近端骨质疏松的建模效果的能力。方法16只8月龄Wistar雌性大鼠(平均体重350g)随机分为模型组(卵巢切除组)与对照组(卵巢假切除组)。术后3个月,取大鼠左侧股骨。应用肢体计算机断层扫描(pQCT)与双能X线骨密度仪(DXA)对骨质疏松建模效果进行对比研究:(1)确定pQCT与DXA测量精度,即计算重复测量的精度误差;(2)比较应用两种骨密度仪所测得的对照组、模型组的骨密度、骨矿含量、骨几何结构参数及其相关系数。结果(1)pQCT总骨及松质骨体密度的测量精度误差分别为2.27%与2.00%,而DXA骨面密度的测量精度误差为3.36%。(2)模型组pQCT总骨体密度和松质骨体密度分别低于对照组8.2%和15.0%犤(模型组-对照组)/对照组×100%犦,差异有显著性(P<0.01);而模型组DXA骨面密度低于对照组3.0%,差异无显著性(P>0.05)。模型组pQCT总骨骨矿含量低于对照组3.7%,差异无显著性(P>0.05),而松质骨骨矿含量低于对照组11.4%,差异有显著性(P<0.05);模型组DXA骨矿含量低于对照组3.0%,差异无显著性(P>0.05)。(3)DXA骨矿含量与pQCT总骨骨矿含量之间呈正相关(r=0.82,P<0.001);DXA骨投影面积与pQCT骨体积之间亦呈正相关(r=0.52,P<0.05);DXA骨面密度与pQCT总骨体密度之间无相关关系(r=0.14,P>0.05)。DXA     

Effect of treadmill exercise on vertebral and tibial bone mineral content and bone mineral density in the aged adult rat: Determined by dual energy X-ray absorptiometry

Summary Dual energy X-ray absorptiometry (DXA; Hologic QDR-1000W) in an ultrahigh-resolution mode, was used to examine the changes in tibial/fibula and vertebral L4 +L5 bone mineral content (BMC) and bone mineral density (BMD) in each 14-month-old female rat at 0, 9, and 16 weeks of study. Twenty rats were randomized by a stratified weight method into two groups, control and exercised. Exercise consisted of running on a flat-bed treadmill, 17 m/minute, 1 hour/day and 5 days/week. As compared with the control group, a significant increase in tibia/fibula BMC and vertebral BMD was apparent at 9 weeks after exercise training (P=0.014 by 2-way analysis of variance). The slope of the gain of the tibia/fibula BMC and BMD by 16 weeks of training was ninefold and fivefold higher than that of the control group (P<0.01 and P<0.05, respectively, by Mann-Whitney test). The correlation coefficient (r) between the final dry weight of excised bone and the final BMC of the intact rat was 0.843 and 0.71 for tibia/fibula and vertebrae, respectively. In summary, we found that in the aged rat, by 9 weeks, exercise increases BMC and BMD in the tibia, whereas in the vertebrae, only increases in the BMD were found. This study demonstrates that this precise and accurate DXA technique is useful in a longitudinal study of in vivo bone mineral changes in the rat over time by taking into account the individual variation between animals as well as changes between groups.     

Effect of High Impact Activity on Bone Mass and Size in Adolescent Females: A Comparative Study Between Two Different Types of Sports

The purpose of this cross-sectional study was to investigate the influence of two different types of weight-bearing activity, muscle strength, and body composition on bone mineral density (BMD), bone mineral content (BMC), and bone area in three different groups of late adolescent girls. The first group consisted of 10 females participating in competitive rope-skipping (age 17.8 ± 0.8 years) training for 6.7 ± 3.1 hours/week; the second group consisted of 15 soccer players (age 17.4 ± 0.8 years) training for 6.1 ± 2.0 hours/week; and the third group consisted of 25 controls (age 17.6 ± 0.8 years) with physical activity of 0.9 ± 1.1 hours/week. The groups were matched for age, height, and weight. BMD (g/cm²), BMC (g), and bone area (cm²) of the total body, lumbar spine, hip, total femur, distal femur, diaphyses of femur and tibia, proximal tibia, and humerus were measured using dual-energy X-ray absorptiometry (DXA). Bone density was also assessed in the radial forearm site of the dominant limb in the rope skippers and in 10 matched controls. The rope skippers had 22% higher BMD at the ultradistal site (P < 0.01). Both high-activity groups had significantly higher BMD (P < 0.05) at most loaded sites compared with the control group. When adjusting for differences in lean mass and starting age of sport-specific training between the activity groups, the rope-skipping group had a higher BMD of the total body, lumbar spine, and right humerus compared with the soccer group. They also had a significantly higher bone area of the total body, total femur, and the proximal femur than both other groups, and a significantly higher bone area of the tibia diaphysis, compared with the soccer group. In a multivariate analysis among all subjects (n = 50), all BMD sites, except the femur diaphysis, distal femur, and proximal tibia, were significantly related to type of physical activity (β= 0.25–0.43, P < 0.05). The bone area values at different sites were strongly related to muscle strength and parameters related to body size [height, weight, lean mass, fat mass, and body mass index (BMI)]. In conclusion, it appears that in late adolescent women, weight-bearing activities are an important determinant for bone density, and high impact activities such as jumping also seem to be associated with a modification of the bone geometry (hence, the bone width) at the loaded sites. Received: 28 June 1999 / Accepted: 22 March 2000