睾丸酮对雄性大鼠类固醇性骨质疏松的影响

目的探讨睾丸酮对雄性大鼠类固醇性骨质疏松的影响。方法30只3月龄雄性SD大鼠,随机分成对照组(A组)、泼尼松组(B组)、睾丸酮(C组)。A组灌生理盐水(4mL·kg-1·d-1),B组予醋酸泼尼松灌胃(4mg·kg-1·d-1),C组灌胃给予甲睾酮(0.2mg·kg-1·d-1)+醋酸泼尼松(4mg·kg-1·d-1),共90d。实验结束后,处死全部大鼠取腰椎和胫骨上段进行不脱钙骨包埋切片,应用计算机自动图像分析系统进行骨组织形态计量学分析。结果与泼尼松组比较,胫骨上端松质骨的%Tb.Ar增加了108%(P<0.01),Tb.N增加了96%(P<0.05),Tb.Sp减少60%;BFR/TV增加了172%(P<0.05),Oc.N减少40.7%(P<0.05);腰椎松质骨的%Tb.Ar增加了52.4%(P<0.05),Tb.Th增加了42%(P<0.05),Tb.Sp减少20%(P<0.05),MAR增加26%(P<0.05)。结论睾丸酮可以有效阻止泼尼松所引起的骨骨质丢失,维持正常的骨质结构。     

康力龙对类固醇性大鼠骨质疏松骨密度和生物力学的影响

目的　从生物力学和骨矿含量测定角度研究康力龙对类固醇性大鼠骨代谢的影响。方法　采用 3月龄雄性SD大鼠 2 8只 ,随机分为基础对照组、年龄对照组、激素模型组和康力龙预防组。后两组给醋酸泼尼松 4 5mg·kg-1,ig ,2次 /周 ;预防组还给康力龙 0 5mg·kg-1·d-1,ig。 3个月后取股骨和第 5腰椎行骨密度测定 ,再行扭转、3点弯曲和压缩试验。结果　与年龄对照组比较 ,激素模型组股骨和第 5腰椎的总骨密度减少了 14 6 4 % (P <0 0 1) ;股骨干在 3点弯曲试验时所承受的载荷减少了17 1% (P <0 0 5 ) ;其余的力学参数都出现减少的趋势。与激素模型组比较 ,康力龙预防组股骨和第 5腰椎的总骨密度有所增加 ;股骨扭转角度明显增加 72 5 % (P <0 0 5 ) ,其余的力学参数都出现增加的趋势。结论　长期使用糖皮生激素 (GC) ,会使大鼠皮质骨和松质骨的骨密度和力学性能下降 ,从而易致骨折 ;应用康力龙则能阻止GC所致骨量丢失 ,还能增加其力学性能。     

ClC-3基因过表达对小鼠骨量和骨结构的影响

 目的: 研究过表达电压门控氯通道家族蛋白成员3(voltage-gated chloride channel family protein 3,ClC-3)基因对小鼠骨骼的影响。方法: 3月龄雄性FVB小鼠用鼠尾基因检测法确定基因型后分为2组:野生型(WT)组和ClC-3过表达(ClC-3 transgene)组,每组各8只。分别测量2组小鼠体重,右侧胫骨长度和重量。取胫骨上段和中段进行脱钙,石蜡包埋,切片,HE染色后,采用骨形态计量学分析胫骨上段松质骨的骨小梁面积百分数(percent trabecular area,%Tb.Ar)、骨小梁数量(trabecular number,Tb.N)、骨小梁宽度(trabecular width,Tb.Wi)、骨小梁分离度(trabecular separation,Tb.Sp)和胫骨中段皮质骨的骨组织总面积(total tissue area,T.Ar)、皮质骨面积(cortical area,Ct.Ar)、皮质骨面积百分数(percent cortical area,%Ct.Ar)、骨髓腔面积(marrow area,Ma.Ar)、骨髓腔面积百分数(percent marrow area,%Ma.Ar)。结果: 小鼠经鼠尾基因检测后确认为野生型或ClC-3过表达型。与WT组相比,ClC-3 transgene组小鼠体重及胫骨长度重量均减小(P<0.05);松质骨的%Tb.Ar和Tb.Wi均减小(P<0.05),Tb.Sp增大(P<0.05),Tb.N的变化无统计学意义;皮质骨的T.Ar、Ct.Ar和%Ct.Ar均减小(P<0.05),%Ma.Ar增大(P<0.05),Ma.Ar的变化无统计学意义。结论: ClC-3过表达导致小鼠的皮质骨和松质骨骨量减少,骨结构变差,提示ClC-3可能参与了骨形成和/或骨吸收。     

镁基植入体植入兔股骨后周围骨微结构变化趋势

目的研究镁基植入体植入兔股骨不同时间点周围骨微结构参数的变化规律。方法将直径2 mm、长7 mm有螺纹及无螺纹的高纯镁(99.99 wt.%)钉植入兔股骨髁,对照组为钻孔组及健康组。在术后8、12、16周进行Micro-CT扫描和分析,得到各组微结构参数,包括:骨质密度(BMD)、骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.Sp)。结果 8周时无螺纹镁钉组BMD、BV/TV显著高于健康组,Tb.N显著高于钻孔组与健康组,Tb.Sp显著低于健康组;12周时有螺纹镁钉组BMD、BV/TV、Tb.N显著高于钻孔组与健康组,Tb.Th显著高于健康者,Tb.Sp显著低于钻孔组与健康组;16周时无螺纹镁钉组的BMD、BV/TV、Tb.N显著高于钻孔组与健康组,Tb.Sp显著低于钻孔组与健康组。结论镁基植入体促使周围骨组织的BMD、BV/TV、Tb.Th、Tb.N更高,Tb.Sp更低,说明其骨整合与骨生长状况良好,镁基植入体能有效促进骨再生。研究结果为镁基植入体的骨科临床应用提供理论依据。     

低蛋白饲料对雄性大鼠胫骨上段和腰椎的骨计量学研究

目的比较低蛋白饲料对大鼠胫骨上段和腰椎松质骨的影响。方法12只3月龄SD雄性大鼠,随机分成正常对照组、低蛋白组LPD(Pr8%)。实验90d时取胫骨上段和第五腰椎行不脱钙骨制片,骨组织形态计量学测量。结果与对照组比,LPD组胫骨上段骨小梁面积百分率(%Tb.Ar)减少(P<0.01),骨结构变差,骨转换率下降;而腰椎松质骨各项指标的变化均无统计学意义。结论低蛋白饲料诱导大鼠胫骨上段骨丢失,而对腰椎骨丢失无明显影响。     

雷公藤甲素通过抑制破骨细胞生成预防骨丢失的研究

目的 探讨雷公藤甲素抗骨质疏松的作用及机制。方法 建立大鼠老年性骨质疏松模型。40只22月龄雄性SD大鼠随机分为雷公藤甲素（每天15μg/kg腹腔注射）治疗组和生理盐水对照组（每天15μg/kg腹腔注射）,连续8周。采用显微CT分析胫骨近端骨松质的骨密度(BMD)和骨显微结构。WB检测成骨相关蛋白表达水平。TRACP-5b染色法测定破骨细胞数,同时检测骨吸收标志物表达水平。结果 显微CT结果显示,雷公藤甲素治疗组大鼠骨密度、骨体积/总体积比值(Bv/Tv)、骨小梁厚度(Tb.Th)、骨小梁数目(Tb.N)、骨小梁间距(Tb.Sp)均显著高于对照组（P<0.05）。两组的成骨相关蛋白表达水平无明显差异,TRACP-5b染色显示雷公藤甲素减少了体内破骨细胞的数量（P<0.05）,同时血液骨吸收标志物水平也明显降低（P<0.05）。结论 雷公藤甲素通过抑制破骨细胞生成进而对老年性骨质疏松有保护作用。雷公藤甲素可能是治疗老年性骨质疏松症的一种可行方案。     

老年人股骨转子间骨折骨活检与骨微结构的临床研究

目的通过对老年人股骨转子间骨折部位进行骨活检与骨微结构研究,了解其骨微结构组织形态学参考值,以指导治疗。方法实验组:选择低、中度能量创伤所致股骨转子间骨折需要手术治疗的男、女性老年病例各15例;对照组:男女各选12例新鲜尸体的股骨标本。用直径为1 cm的环钻于股骨转子间区按统一标准定位后,钻取高2 cm、直径1 cm的圆骨柱,进行骨活检与骨微结构组织形态观察和计量分析。结果老年人股骨转子间骨小梁连接减少从而整个小梁逐渐丧失,在一定宽度(mm)条件下骨小梁较稀疏,骨小梁面积占骨组织面积的百分率较小,两个骨小梁之间的平均距离较大,骨小梁结点相对较少,而骨小梁游离末端数相对多。两组间Tb.N、Tb.Wi、Tb.Sp、%Tb.Ar、N/F比较,差异均有统计学意义(P<0.05)。结论老年人股骨转子间区骨微结构组织形态参数值对抗骨质疏松治疗及合适的功能锻炼具有重要指导意义。     

血管内皮生长因子对尾吊大鼠后肢胫骨骨丢失的影响

目的探究血管内皮生长因子(vascular endothelial growth factor,VEGF)对废用性骨丢失的影响。方法建立尾吊大鼠的动物模型,并随机平均分为尾吊盐水组、尾吊VEGF组、对照盐水组、对照VEGF组。实验过程中,每周两次对大鼠右腓肠肌注射VEGF或者等量的生理盐水,4周后通过micro-CT对大鼠胫骨近端进行扫描,以松质骨和皮质骨骨密度(bone mineral density,BMD)、骨体积分数(BV/TV)、骨小梁数量(Tb.N)、骨小梁间距(Tb.Sp)和结构模型指数(SMI)等松质骨微结构参数以及皮质骨厚度作为评价指标,探讨VEGF对尾吊大鼠后肢胫骨骨丢失的影响。结果与对照组大鼠相比,尾吊组大鼠松质骨表观BMD、BV/TV、Tb.N以及皮质骨厚度均显著降低,Tb.Sp与SMI显著升高,尾吊会造成大鼠的骨丢失,而注射VEGF能够缓解尾吊大鼠松质骨的骨丢失。结论血供的改变可能与骨重建之间存在着一定的联系,改善血供有助于对抗废用性的骨丢失。     

血管内皮生长因子对尾吊大鼠后肢胫骨骨丢失的影响

目的 探究血管内皮生长因子（vascular endothelial growth factor, VEGF）对废用性骨丢失的影响。方法 建立尾吊大鼠的动物模型,并随机平均分为尾吊盐水组、尾吊VEGF组、对照盐水组、对照VEGF组。实验过程中,每周两次对大鼠右腓肠肌注射VEGF或者等量的生理盐水,4周后通过micro-CT对大鼠胫骨近端进行扫描,以松质骨和皮质骨骨密度（bone mineral density, BMD）、骨体积分数(BV/TV)、骨小梁数量(Tb.N)、骨小梁间距(Tb.Sp)和结构模型指数(SMI)等松质骨微结构参数以及皮质骨厚度作为评价指标,探讨VEGF对尾吊大鼠后肢胫骨骨丢失的影响。结果 与对照组大鼠相比,尾吊组大鼠松质骨表观BMD、BV/TV、Tb.N以及皮质骨厚度均显著降低,Tb.Sp与SMI显著升高,尾吊会造成大鼠的骨丢失,而注射VEGF能够缓解尾吊大鼠松质骨的骨丢失。结论 血供的改变可能与骨重建之间存在着一定的联系,改善血供有助于对抗废用性的骨丢失。     

血管内皮生长因子对尾吊大鼠后肢胫骨骨丢失的影响

目的 探究血管内皮生长因子（vascular endothelial growth factor, VEGF）对废用性骨丢失的影响。方法 建立尾吊大鼠的动物模型,并随机平均分为尾吊盐水组、尾吊VEGF组、对照盐水组、对照VEGF组。实验过程中,每周两次对大鼠右腓肠肌注射VEGF或者等量的生理盐水,4周后通过micro-CT对大鼠胫骨近端进行扫描,以松质骨和皮质骨骨密度（bone mineral density, BMD）、骨体积分数(BV/TV)、骨小梁数量(Tb.N)、骨小梁间距(Tb.Sp)和结构模型指数(SMI)等松质骨微结构参数以及皮质骨厚度作为评价指标,探讨VEGF对尾吊大鼠后肢胫骨骨丢失的影响。结果 与对照组大鼠相比,尾吊组大鼠松质骨表观BMD、BV/TV、Tb.N以及皮质骨厚度均显著降低,Tb.Sp与SMI显著升高,尾吊会造成大鼠的骨丢失,而注射VEGF能够缓解尾吊大鼠松质骨的骨丢失。结论 血供的改变可能与骨重建之间存在着一定的联系,改善血供有助于对抗废用性的骨丢失。     

复方丹参对高脂大鼠模型骨形态计量学参数的影响

背景：复方丹参对抗泼尼松性大鼠的骨丢失具有抑制骨吸收作用,但对高脂血症所致的骨质疏松症效果如何未见报道。 目的：通过骨形态计量学观察复方丹参对大鼠胫骨和腰椎骨丢失的防治作用。 方法：用脂肪乳剂建立高脂血症骨丢失大鼠模型,30只SD大鼠随机数字表法分为3组,正常对照组、高脂乳剂组、复方丹参组,分别给予生理盐水、高脂乳剂、高脂乳剂和复方丹参,连续16周。 结果与结论：与高脂乳剂组相比,复方丹参可使高脂大鼠胆固醇明显降低和高密度脂蛋白胆固醇明显升高,可以有效改善高脂乳剂导致的脂质代谢紊乱。复方丹参组的骨小梁面积百分数、骨小梁数量、成骨细胞贴壁长度百分率均增加(P < 0.05),而骨小梁分离度、每毫米破骨细胞数、破骨细胞贴壁长度百分率均减少(P < 0.01),反映骨形成及骨矿化的指标变化不明显;胫骨中段的皮质骨面积百分数增加(P < 0.01),骨髓腔面积百分数减少(P < 0.01),骨内外膜的形成和矿化均无明显变化;腰椎松质骨的骨小梁面积百分数、骨小梁数量、骨小梁宽度增加(P < 0.05)、而骨小梁分离度减少(P < 0.01)。提示长期高脂乳剂灌胃会导致大鼠骨量丢失,复方丹参能有效对抗高脂大鼠胫骨上段、中段骨、第5腰椎的骨丢失。     

芪霍肾宝抗泼尼松所致大鼠松质骨结构破坏的作用

目的：观察芪霍肾宝对糖皮质激素引起松质骨结构破坏的防治作用。方法：选用3月龄SD雄性大鼠24只，随机分为对照组、激素组和治疗组。激素组用泼尼松4.5mg/kg灌胃．每周二次；治疗组给予芪霍肾宝O.38g/kg，每周6次．持续90天。扫描电镜观察大鼠腰椎松质骨结构的改变。结果：与正常组比较，激素组的大鼠骨小梁变少．变细，断裂，连接不紧密．表面常见骨吸收形成的陷窝；治疗组大鼠骨小梁粗大．排列整齐，连接紧密。结论：芪霍肾宝能有效防止糖皮质激素所引起的松质骨三维结构的损害，保持骨的正常力学强度，避免骨折。     

大鼠实验性骨质疏松的扫描电镜观察

目的；探讨大鼠卵巢切除后和泼尼松所致骨质疏松时松质骨结构的改变。方法；切除雌性大鼠双侧卵旭及用泼尼松给雄性大鼠灌胃，分别制成绝经后骨质疏松和类固醇性骨质疏松动物模型。在扫描电镜下，观察大鼠股骨及腰椎松质骨结构的改变。结果：与正常组比较，骨质疏松的大鼠骨小梁变小，变细，断裂，连接中断，表面常见骨吸收形成的陷窝。结论：切除卵巢和泼尼松所致的骨质疏松均可造成松质骨三维结构的损害，使力学强度降低，增加骨折     

睾丸酮与葡萄糖酸钙联合用药对类固醇性骨质疏松雄性大鼠骨代谢的影响

目的探讨睾丸酮与葡萄糖酸钙联合用药对类固醇性骨质疏松雄性大鼠骨代谢过程的影响。方法30只3月龄SD雄性大鼠,随机分成年龄对照组(A组)、泼尼松组(B组)、实验组(C组)。A组予生理盐水灌胃(4mL.kg-1.d-1),B组予醋酸泼尼松灌胃(4mg.kg-1.d-1),C组灌胃给予甲睾酮(0.2mg.kg-1.d-1)+葡萄糖酸钙(0.5mg.kg-1.d-1)+醋酸泼尼松(4mg.kg-1.d-1),共90d。实验结束后,处死全部大鼠,取尺骨和血清做生化指标测定。结果B组大鼠尺骨羟脯氨酸的含量无显著变化,骨钙、骨磷、骨锌的含量显著降低;血钙显著升高,碱性磷酸酶含量降低。C组大鼠骨钙、骨磷、骨锌含量较B组显著升高;血钙降低恢复正常,碱性磷酸酶浓度升高,各项指标均接近正常对照组水平。结论睾丸酮与葡萄糖酸钙联合应用可以有效地防治泼尼松引起的雄性大鼠骨代谢紊乱。     

卵巢切除及雌二醇对大鼠腰椎松质骨微结构的作用及其生物力学性能的分析

应用micro-CT获得腰椎松质骨微结构的三维参数,分析卵巢切除术与雌二醇干预对大鼠松质骨微结构及整体骨生物力学性能的作用,初步讨论松质骨微结构的改变对生物力学性能的影响.6月龄未交配雌性SD大鼠30只,随机分成3组(每组10只):假手术对照组(Sham)、去卵巢组(OVX)和去卵巢 补充雌二醇组(EBT).术后相同条件饲养5个月,取第3腰椎进行生物力学压缩试验,第4腰椎行micro-CT扫描.结果表明,与相应的Sham组比较,OVX组的BV/TV、Tb.N均明显下降,Tb.Sp和SMI明显增高.EBT组的BV/TV、Tb.N和Tb.Th均大于OVX组,Tb.Th和SMI明显小于OVX组.骨力学性能检测显示OVX组腰椎松质骨E、Fmax和σmax均明显降低,而EBT组上述骨生物力学参数均明显改善.通过micro-CT获得的骨微结构参数并结合骨力学性能检测能为合理评价骨质疏松及抗骨质疏松药物药效研究提供较好的实验依据.     

The healing of confined critical size cancellous defects in the presence of silk fibroin hydrogel

In vitro and in vivo behaviour of an injectable silk fibroin (SF) hydrogel was studied through osteoblast cultures and after implantation in critical-size defects of rabbit distal femurs. A commercial synthetic poly(D,L lactide-glycolide) copolymer was used as control material. In vitro biocompatibility was evaluated by measuring LDH release, cell proliferation (WST1), differentiation (ALP, OC), and synthetic activity (collagen I, TGF ss1, IL-6). Bone defect healing rate and quality of the newly formed bone inside the defects were determined in vivo by measuring trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), mineral apposition rate (MAR) and bone formation rate (BFR/B.Pm). In vitro tests indicated that both materials significantly increased cell proliferation in comparison with the negative control. A significant increase in the TGF-beta1 level was found for SF hydrogel in comparison with the control material and negative control. Both materials promoted bone healing when used to fill critical size defects in rabbit femurs. The new-formed bone of the SF hydrogel treated defects showed significantly higher BV/TV, Tb.Th, MAR and BFR/B.Pm and lower Tb.Sp values in comparison with the control gel. At 12 weeks the re-grown bone of the SF hydrogel-treated defects appeared more similar to normal bone than that of the control synthetic polymeric material-treated defects, except for the Tb.N value that differed significantly from that of normal bone (p<0.05). MAR and BFR/B.Pm presented significantly (p<0.05) higher values for SF hydrogel-treated defects in comparison with controls treated with a synthetic polymeric material, confirming that SF hydrogel accelerated remodelling processes.     

Comparison of the effects of heparin and the direct factor Xa inhibitor,rivaroxaban, on bone microstructure and metabolism in adult rats

Aim: Deep venous thrombosis is a significant complication following surgery, and is associated with high morbidity and mortality in adults. The direct factor Xa inhibitor, rivaroxaban, is used to prevent venous thromboembolism in patients suffering from trauma and joint arthroplasty. The present study compared the effects of rivaroxaban and heparin on bone microstructure and metabolism in adult rats.

Materials and methods: Twenty-four Wistar rats were divided into sham, rivaroxaban and heparin groups. Rivaroxaban (1.5?mg·kg^?1·d^?1) and heparin (2?IU·g^?1·d^?1) were administered for 4 weeks. To assess changes in bone metabolism, serum calcium and phosphorus levels, and bone formation and resorption markers were examined. Micro-CT analysis was used to examine the microstructure of both trabecular and cortical bone. Dual energy X-ray absorptiometry was employed to detect bone mineral density (BMD).

Results: Serum phosphorus levels were significantly lower in both rivaroxaban (1.33?±?0.07?mmol/L) and heparin (1.33?±?0.21?mmol/L) rats than in sham rats (1.71?±?0.14?mmol/L). Activity and levels of bone formation markers, bone-specific alkaline phosphatase (BAP) and type I procollagen N-terminal pro-peptide (PINP), were 32.4 and 38.2% lower in heparin-treated rats than in sham rats. Bone resorption markers, pyridinoline (PYD) and deoxypyridinoline (DPD), were 20.1 and 34.3% higher in heparin-treated rats than in sham rats, respectively. By contrast, rivaroxaban only resulted in a decrease PINP levels. Bone volume fraction (BV/TV) decreased by 23.5 and 20.5% from those in sham rats, while trabecular separation (Tb.Sp) increased by 28.2 and 16.3% in trabecular bone of rivaroxaban- and heparin-treated rats, respectively. Moreover, the microstructure of cortical bone and BMD were negatively affected by heparin but not by rivaroxaban.

Conclusion: Rivaroxaban leads to fewer adverse effects on bone microstructure than heparin.     

Effects of daily administration of prostaglandin E2 and its withdrawal on the lumbar vertebral bodies in male rats.

The effects of daily prostaglandin E2 (PGE2) treatment (on) and PGE2 treatment followed by withdrawal (on-off) on cancellous bone in lumbar vertebral bodies were studied in 7-month-old male Sprague-Dawley rats. The first groups of rats were given daily subcutaneous injections of 0, 1, 3, and 6 mg PGE2/kg/d for 60, 120, and 180 days, and the second group of rats were given PGE2 for 60 days followed by withdrawal for 60 and 120 days. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified sections of fourth lumbar vertebral bodies. Systemic PGE2 treatment elevated cancellous bone mass of lumbar vertebral bodies 26-60% above control levels within 60 days and continued treatment maintained it for another 120 days, but the excess bone was lost after the treatment was withdrawn. PGE2 treatment for 60 days increased trabecular bone area, trabecular width, and bone formation parameters, and shortened remodeling periods in a dose-response manner. These changes were sustained at the levels achieved by 60-day treatment in the rats treated for 120 and 180 days. The eroded perimeter increased at day 60 and further at day 120 and then plateaued. In the on-off treated rats, the cancellous bone area, bone formation, and resorption parameters returned to near age-related controls by 60 days after withdrawal and were maintained there after 120 days of withdrawal. Therefore we conclude that the continuous treatment is needed in order to maintain the PGE2-induced bone gain. When these findings were compared to those previously reported for the proximal tibial metaphyses, we found that the proximal tibial spongiosa was much more responsive to PGE2 treatment than the fourth lumbar vertebral body.