强骨康疏胶囊对去卵巢骨质疏松大鼠骨细微结构及骨代谢的影响

目的:观察强骨康疏胶囊对去卵巢骨质疏松大鼠的骨密度、OPG及RANKL蛋白表达、骨组织形态计量学参数及骨组织细微结构的影响。方法:制备去卵巢骨质疏松大鼠模型后,分组:正常对照组、模型空白组、中药低剂量预防组、中药高剂量预防组、雌激素预防组。给药1月后,检测各组股骨骨密度值,显微镜下观察股骨骨小梁的结构变化,并检测骨组织形态计量学参数。采用免疫组织化学染色法检测大鼠股骨OPG及RANKL蛋白表达。结果:模型空白组大鼠股骨骨密度减少,骨小梁厚度、面积、面积百分数均减少,骨小梁间距增大,股骨OPG蛋白平均光密度值显著降低,RANKL蛋白平均光密度值明显增高;雌激素预防组、中药低剂量组、中药高剂量组对上述指标均有明显改善。结论:强骨康疏胶囊能有效提高骨量,维持骨小梁立体空间结构,改善大鼠股骨远端松质骨的显微结构,能够提高骨OPG蛋白表达及抑制RANKL蛋白表达。     

毛蕊异黄酮防治去卵巢大鼠骨质疏松的实验研究

目的复制去卵巢大鼠骨质疏松动物模型,观察不同剂量的毛蕊异黄酮对去卵巢大鼠骨质疏松的防治作用。方法 50只SD雌性大鼠,随机分成五组：设一假手术组;腹腔手术切除大鼠双侧卵巢,分为阴性对照组、毛蕊异黄酮低、高剂量组和雌激素对照组,分别给予标准饲料和不同剂量受试物,12周后进行骨密度、骨组织形态计量、生物力学测定,与雌激素对照,观察给与毛蕊异黄酮对绝经后骨质疏松的防治作用。结果大鼠去卵巢后骨密度显著下降,股骨的力学性能有较大变化,弯曲强度和弯曲弹性模量明显降低。给予毛蕊异黄酮后,可使骨密度显著提高（P〈0.01）,存在一定的剂量-效应关系,同时弯曲强度和弯曲弹性模量明显增加,但均低于雌激素对照组。结论通过去卵巢手术,成功建立绝经后骨质疏松动物模型;毛蕊异黄酮对去卵巢大鼠具有显著的骨保护效应,并存在一定的剂量效应关系,其作用弱于雌激素。     

去卵巢山羊长骨生物力学性能的变化

采用生物力学方法研究雌性山羊双侧卵巢切除后１８０天其长骨生物力学性能的变化。１５±岁雌性成都山羊１０只，体重２２±ｋｇ，随机分为对照组（Ｃｏｎｔｒｏｌ５只）和双侧卵巢切除组（ＯＶＸ５只）。术后１８０天处死动物，取出双侧股，胫，跖，肱，桡和掌骨。用三点弯曲法测整体骨弯曲结构力学性能的变化。分别取断端密质骨，用三点弯曲，压缩和拉伸方法测骨试件的材料力学特性的变化。结果显示：与对照组比较，双侧卵巢切除组各长骨相应的骨密度，断端骨组织厚度和整体三点弯曲的破坏荷载均明显下降（Ｐ＜００５）；除股骨外，各长骨的整体三点弯曲极限强度，弹性模量和骨试件的弯曲与压缩极限强度，弹性模量以及部分长骨拉伸极限强度明显低于对照组（Ｐ＜００５）。本研究结果提示：雌性山羊双侧卵巢切除后１８０天，其长骨的整体抗弯强度和骨试件的抗弯，抗压，以及抗拉强度均有不同程度的下降，易于骨折。这与临床绝经后妇女雌激素降低，导致骨质疏松，使骨折的倾向性增大是一致的；也与大鼠双侧卵巢切除骨质疏松模型所表现出的骨结构变化和骨量减少相符合。作者认为，骨生物力学参数是评价骨质疏松的重要指标。切除双侧卵巢的雌性山羊有可能成为骨质疏松的大动物模型。     

可注射硫酸钙修复骨质疏松大鼠股骨近端骨小梁的实验研究*

目的探讨可注射硫酸钙植入对骨质疏松大鼠股骨近端骨小梁的影响。方法复制去卵巢大鼠骨质疏松模型,采用穿刺注射技术将可注射硫酸钙植入骨质疏松实验大鼠股骨近端,对侧做自身对照,于术后2、4、8、12周取材,对双侧股骨近端行影像学、组织学观察,骨组织形态计量学及双能x线骨密度测定。结果影像学显示：术后4、8、12周实验侧股骨近端密度明显高于对照侧。骨组织学检查显示：术后4周实验侧硫酸钙降解,出现成骨效应;8周股骨近端穿刺注射区域已为致密、分化不成熟的骨小梁所填充;12周股骨近端骨小梁得到较好修复,为成熟的骨小梁组织所填充;对照侧为典型骨质疏松病理改变。骨组织形态计量学测定显示：术后8和12周实验侧骨小梁面积百分数、骨小梁宽度和骨小梁数量显著高于对照侧,实验侧骨小梁分离度显著小于对照侧。术后2、4、8、12周实验侧股骨近端骨密度较对照侧明显增加。结论可注射硫酸钙能快速有效的修复骨质疏松大鼠股骨近端骨小梁。     

绝经后骨质疏松症模型体视学测量和机理初探

目的:观测去势术后大鼠骨组织体视学的改变,复制绝经后骨质疏松症的动物模型,初步探讨骨质疏松症的发病机制。方法:将31只3月龄雌性SD大鼠随机分为卵巢切除术组(OVX)和假手术组(sham),术后28d和56d分别处死。测量子宫湿重,骨矿物密度(BMD)和骨组织形态计量参数,分析骨组织微结构的变化。结果:OVX组术后28d和56d大鼠子宫湿重和股骨远端1/3处骨密度均显著少于sham组(P＜0.05);OVX组股骨远端和胫骨近端的干骺端骨小梁面积百分率显著少于sham组(P＜0.01)。结论:卵巢切除术后大鼠股骨远端骨矿物密度和骨组织形态计量学参数稳步下降,胫骨近端骨矿物密度和骨组织形态计量学参数迅速下降而且不稳定;雌激素减少导致的骨质疏松主要发生在长骨的干骺端,骨骺受影响较少;骨组织形态计量参数中骨小梁面积百分比敏感性和稳定性较高。     

短程与长程去卵巢大鼠骨计量学的实验研究

目的：探讨３月龄ＳＤ大鼠去卵巢短程和长程骨明的变化，以指导临床用药。方法：３０只３月龄龄ＳＤ雌性大鼠，随机分为基础对照组、年龄对照组、去卵巢组，切除双侧卵巢建立骨质疏松以症模型，实验结束，取有近端行为不脱钙骨制片进行骨组织形态计量学分析。结果：实验３０天去卵巢大鼠与年龄对照，骨形成的参数值和骨吸收的参数值都明显增加。但骨吸收大于骨形成，造成骨量丢失，骨结构变差，９０天去卵巢大鼠组与对照组比较，荧光     

植物雌激素对去卵巢大鼠骨质疏松性骨折愈合的影响

目的观察植物雌激素对卵巢去势大鼠骨折愈合过程中骨痂骨密度的影响。方法复制卵巢去势大鼠骨质疏松模型并制造股骨中段闭合性骨折,然后进行克氏针髓腔内固定,观察大鼠骨折内固定后骨痂与近骨痂段股骨骨密度的变化。结果异黄酮组、雌二醇组和假手术组骨痂的骨密度高于无用药组,差异具有统计学意义(P<0.05);而异黄酮组、雌二醇组和假手术组之间没有显著差别。结论植物雌激素能够显著提高骨质疏松大鼠骨痂及近骨痂段骨组织的骨密度、促进骨折愈合,与雌二醇组作用相近。     

去卵巢大鼠骨组织的变化

目的：观察去卵巢对大鼠骨组织的改变，以建立妇女绝经后骨质疏松的动物模型。方法：选用３月龄ＳＤ雌性大鼠１６只，随机分为对照组和去卵巢组。去卵巢组的大鼠的双侧卵巢被切除，对照组做假手术，持续９０天。用骨矿测定仪测量大鼠股骨的骨密度及在半自动图像分析仪观测胫骨近端骨小梁的静、动态指标，并在扫描电镜下观察大鼠股骨松质骨结构的改变。结果：与对照组比较，去卵巢组大鼠股骨远端的骨密度明显降低。胫骨骨小梁的面积减     

去卵巢大鼠骨组织的变化

目的:观察去卵巢对大鼠骨组织的改变,以建立妇女绝经后骨质疏松的动物模型。方法:选用3月龄SD雌性大鼠16只,随机分为对照组和去卵巢组。去卵巢组的大鼠的双侧卵巢被切除,对照组做假手术,持续90天。用骨矿测定仪测量大鼠股骨的骨密度及在半自动图像分析仪观测胫骨近端骨小梁的静、动态指标,并在扫描电镜下观察大鼠股骨松质骨结构的改变。结果:与对照组比较,去卵巢组大鼠股骨远端的骨密度明显降低。胫骨骨小梁的面积减少,骨小梁间隙增加。股骨的骨小梁减少,变细,断裂,连接不紧密,表面常见骨吸收形成的陷窝。结论:用切除卵巢的方法造成雌激素缺乏,导致骨质疏松,是研究因绝经引起原发性骨质疏松的可靠动物模型。     

去卵巢大鼠骨组织的变化

目的:观察去卵巢对大鼠骨组织的改变,以建立妇女绝经后骨质疏松的动物模型。方法:选用3月龄SD雌性大鼠16只,随机分为对照组和去卵巢组。去卵巢组大鼠的双侧卵巢被切除,对照组做假手术,持续90天。用骨矿测定仪测量大鼠股骨的骨密度及在半自动图像分析仪观测胫骨近端骨小梁的静、动态指标,并在扫描电镜下观察大鼠股骨松质骨结构的改变。结果:与对照正常组比较,去卵巢组大鼠股骨的远端的骨密度降低(P<0.05)。胫骨骨小梁的面积减少,骨小梁间隙增大。股骨的骨小梁变少,变细,断裂,连接不紧密,表面常见骨吸收形成的陷窝。结论:用切除卵巢的方法造成雌激素缺乏,导致骨质疏松,作为研究因绝经引起的原发性骨质疏松的可靠动物模型。     

去卵巢大鼠椎骨组织形态计量学、生物力学特点及相关性研究

采用骨组织形态计量学、骨生物力学和骨矿含量测定等方法研究 10 .5月龄至 16月龄 SD大鼠和双侧卵巢去除术后椎骨的骨质量变化以及它们之间的相关关系。雌性 SD大鼠随机分为 6组 :(1) 10 .5月龄基础组 ;(2 )13月龄假手术组 (sham - 1) ;(3) 13月龄去卵巢组 (OVX- 2 ) ;(4) 16月龄假手术组 (sham - 2 ) ;(5 ) 16月龄去卵巢组(OVX- 2 )和 (6 )雌激素治疗组 :去卵巢 10周后给予雌激素治疗 12周 (OVX- 2 +EE)。所有大鼠在处死前 14、13d和4、3d分别皮下注射四环素和钙黄绿素作体内荧光标记。实验终止时取大鼠第 4腰椎行骨组织形态计量学测量 ,第5腰椎体作试件压缩试验 ,试验后的椎体进行骨矿物元素测定。结果发现 10 .5月龄至 16月龄大鼠椎体骨干重、冠状径、骨小梁面积骨小梁厚度有增加趋势 ,骨的破坏荷载 ,破坏应力和弹性模量也有增加趋势 ,以 13月龄为高峰值。去卵巢 10周后 ,上述指标明显下降 ,2 2周后 ,下降更明显。雌激素治疗后上述指标明显改善。相关研究表明 ,骨小梁面积与骨的破坏应力呈正相关 (P<0 .0 5 ) ,而骨的破坏应力又与骨矿 (主要成分 Ca)含量呈正相关 (P<0 .0 1)。去卵巢后 ,骨小梁面积的下降比骨破坏应力的下降更明显 ,出现的时间更早。本研究表明 ,骨组织形态计量学检测和骨生物力学检     

Effects of raloxifene on bone density,biomarkers, and histomorphometric and biomechanical measures in ovariectomized cynomolgus monkeys

OBJECTIVE: The purpose of this study was to determine the effect of raloxifene on bone density, strength, metabolism, and histomorphometric characteristics in ovariectomized cynomolgus monkeys. DESIGN: A prospective, longitudinal study was designed to examine the effects of conjugated equine estrogens (0.04 mg/kg, CEE) and raloxifene (1 or 5 mg/kg, R1 and R5, respectively) on bone density, biomarkers, histomorphometry, and strength. Control groups included ovariectomized and sham-operated monkeys. Treatment was initiated the day after ovariectomy and continued for 24 months. Bone biomarker data were collected at baseline and every 3 months after surgery. Bone mass was determined at baseline and every 6 months after ovariectomy. Iliac biopsies were collected at baseline and 16 months postovariectomy, and the second lumbar vertebra and left midshaft femur collected at necropsy were examined histomorphometrically. Bone biomechanical properties were determined for the right femur and vertebrae. RESULTS: Compared with the placebo-treated ovariectomized monkeys, the high-dose raloxifene group had lower levels of alkaline phosphatase, tartrate-resistant acid phosphatase, urinary CrossLaps (collagen degradation products), and greater bone mass in the lumbar vertebrae. In the endocortical compartment, the high-dose raloxifene group had significantly lower mineralizing surface, mineral apposition rate, and bone formation rate in the iliac biopsy collected at 16 months and lower bone formation rate in the second lumbar vertebra. Within the midshaft femur, low-dose raloxifene significantly decreased the osteonal and total bone formation rates and also prevented the decrease in Young's modulus induced by ovariectomy in the midshaft femur. CONCLUSIONS: High-dose raloxifene prevented the development of osteopenia in the ovariectomized monkey by reducing bone turnover, albeit to a lesser extent than CEE. Histomorphometric and biomarker data suggest that mechanisms underlying the effect of raloxifene differ somewhat from that of CEE.     

去势大鼠5种骨转换生化指标的动态变化

目的： 对去势大鼠骨质疏松动物模型形成过程中5种骨转换指标的变化及其相关性进行研究。方法: 将3月龄SD雌性大鼠分为3组：切除卵巢组(OVX)，假手术组(sham)和对照组(control)，术前和术后分别于1、1.5、2、2.5、3和4月检测血清骨钙素(OC)、碱性磷酸酶(ALP)、 骨碱性磷酸酶(BALP)、抗酒石酸酸性磷酸酶(TRAP)和羟脯氨酸(HYP)水平，并作大鼠胫骨病理切片检查。结果: OVX组血清OC、ALP、BALP、TRAP和HYP水平均明显高于sham组，其变化顺序依次为：TRAP/HYP→OC→ALP/BALP；5种指标之间呈显著正相关；术后3月OVX组大鼠胫骨小梁结构有病理改变。结论: 去势大鼠属于高转换型骨质疏松；在模型形成过程中，骨吸收指标的变化早于骨形成指标的改变；骨转换指标是反映绝经后早期骨量丢失的灵敏指标。     

Ovariectomy-associated changes in bone mineral density and bone marrow haematopoiesis in rats

The relationship between the bone mass loss and bone marrow haematopoiesis in osteoporosis remains obscure. We selected 3-month-old female Sprague–Dawley rats and randomly divided them into six groups. Three groups were ovariectomized (OVX), while the other three groups were sham operated (Sham). Four, 8 and 12 weeks after the surgical procedure, the rats were euthanized and sampled. The left femur was used for measurement of bone mineral density (BMD). The right femur distal metaphysic cancellous bone was processed for morphological evaluation. Our results showed that the femur BMD in the 4-week OVX group was not significantly decreased compared with that of the 4-week Sham group, but that the volume of adipose tissue in the bone marrow was markedly increased. The femur BMD in the 8-week OVX group was decreased significantly compared with that of the 8-week Sham group ( P   <   0.05). Meanwhile, the volume of haematopoietic tissue decreased and the volume of adipose tissue increased. The number of megakaryocytes was decreased ( P   <   0.05). Interestingly, the osteoclasts and mast cells were increased in number in the 8-week OVX group ( P   <   0.05). These changes became obvious in the 12-week OVX rats, in contrast to the Sham groups. The volume of trabecular bone and the number of osteoblasts in the 12-week OVX group decreased significantly. Increased reticulin fibres were observed only in the 12-week OVX group. Our studies demonstrated a reciprocal correlation between bone-forming osteoblasts and marrow adipose tissue and suggest that OVX rats may be valuable as an animal model to study hypohaemopoiesis.     

Curculigo orchioides, a traditional Chinese medicinal plant, prevents bone loss in ovariectomized rats

OBJECTIVE: Natural medicines derived from plants have aroused increasing interest in the prevention and treatment of osteoporosis. This is due to their unique characteristics as these are more suitable for long-term use compared with synthesized chemicals and have apparently fewer adverse effects. Curculigo orchioides (CO) has a long history in the treatment of postmenopausal osteoporosis in traditional Chinese medicine. The present study was designed to investigate the protective effects of ethanol extracts of CO on ovariectomy-induced bone loss. METHODS: Sixty female (4.5-month-old) Sprague-Dawley rats were assigned to sham and OVX groups. The OVX rats were further divided into five subgroups treated respectively, with vehicle, nylestriol (1 mg/kg, i.g.) and CO extract (0.5, 1.0, and 2.0 g/kg, i.g.) for 12 weeks. Bone mineral density (BMD) and bone mineral content (BMC) were measured by peripheral quantitative computerized tomography (pQCT) densitometry. Serum phosphorus, calcium, ACTH, corticosterone, deoxypyridinoline crosslinks to creatinine ratio (DPD/Cr), alkaline phosphate (ALP), tartrate-resistant acid phosphatase (TRAP), osteoprotegerin (OPG), IL-6, and TNF-alpha were also determined. RESULTS: Administration of CO extract prevented bone loss in the trabecular bone of the tibia in ovariectomized rats without affecting the weight of the body and the uterus, and increased serum phosphorus, calcium, and OPG levels, decreased serum DPD/Cr, TRAP, ACTH, and corticosterone levels, but did not alter serum TNF-alpha, IL-6, and ALP levels in ovariectomized rats. CONCLUSION: CO ethanol extract has a definite protective effect on bone loss in ovariectomized rats by inhibiting bone resorption and increasing serum phosphorus and calcium levels, without affecting bone formation. Therefore, CO can be considered a potential antiosteoporosis herbal plant, although more studies are needed to clarify its real potential chemical constituents and their mechanism of action.     

The effect of ovariectomy combined with hindlimb unloading and reloading on the long bones of mature Sprague-Dawley rats

OBJECTIVE: To determine the effect of loss of ovarian function and mechanical loading (ie, inactivity) alone or in combination on bone mass and strength. DESIGN: Mature (aged 6 mo) rats were ovariectomized to induce loss of ovarian function and bone. Hindlimb unloading (HLU) was used to determine the effect of mechanical unloading and reloading on bone mass and strength. Bone mass of the femur and tibia was determined using dual-energy x-ray absorptiometry. Femoral and tibial bone strength was determined by a three-point bending test and by a torsion test. RESULTS: Ovariectomy (OVX) alone decreased total bone mineral density (BMD) in the femur (-5.5%, P=0.03) and tibia (-7.3%, P=0.01) compared with that for sham-operated animals. HLU alone for 4 weeks had no significant effect on bone. Together OVX/HLU accentuated BMD loss in the femur (-10.5%, P<0.01) compared with that for sham-operated animals. The femur was more sensitive than the tibia to the combination of OVX/HLU, indicated by the reduction (-5.3%, P<0.05) of total BMD below that achieved by OVX alone. Torsion tests showed that OVX/HLU but not OVX or HLU alone reduced bone strength. There was a correlation between lower femoral total BMD (r2=0.65, P<0.001) and reduced torque strength. Bone loss did not continue during the 2 weeks of reloading. CONCLUSIONS: OVX accompanied by mechanical unloading results in more rapid and severe bone loss than either OVX or unloading alone and therefore is associated with a greater likelihood of osteoporosis.     

磁场对去卵巢大鼠骨密度、骨强度和骨代谢的影响

本文研究了旋转恒定磁场对去卵巢大鼠骨密度，骨强度和骨代谢的影响。结果表明磁场处理30分钟且加钙组的骨密度，能量吸收，弹性能量吸收，最大载荷，最大桡度和弹性桡度等指标均显著高于去卵巢组，分别增加3.5%,15.4%,12.4%,7.6%,5.8%,11.9%t 5.2%。其碱性磷酸酶，血磷，血钙等指标也比去卵巢组分别高71％，108％，156％。实验还检测了暴磁1个月及停止暴磁后1到2个月，大鼠骨密度和骨矿含量的变化，结果表明磁场处理存在着窗口效应和滞后效应。