去卵巢大鼠椎骨组织形态计量学与骨矿含量的T型关联度分析

目的:运用T型关联度分析,探讨去卵巢大鼠椎骨组织形态计量学与骨矿含量之间的相关关系方法:10.5月龄未交配的雌性SD大鼠40只,随机分为5组:10.5月龄基础对照组(Basal);13月龄假手术组(Sham1);13月龄去卵巢10周组(OVX1);16月龄假手术组(Sham2);16月龄去卵巢22周组(OVX2)。所有大鼠灌喂生理盐水5ml·kg-1·d-1实验终止时取第4腰椎进行骨组织形态计量学测量,第5腰椎进行骨矿物质含量测定,通过T型关联度计算,分析骨矿含量对骨组织形态计量学各参数的影响。结果:去卵巢大鼠腰椎骨矿含量与骨组织形态计量学静态参数(骨小梁面积百分数、骨小梁厚度)成正相关,而与动态参数(骨转换率)成负相关其中骨钙、骨磷的含量对骨形态计量学参数的影响较大。结论:T型关联度分析可客观地、公正地评价去卵巢大鼠椎骨组织形态计量学与骨矿含量之间的相关关系。     

替勃龙治疗去势大鼠骨质疏松症的研究

目的探讨替勃龙对去势大鼠骨质疏松症的治疗效果。方法选用3月龄雌性W istar大鼠按体重随机分为假手术组、模型组、替勃龙组、雌激素组4组,假手术组和模型组每天等量赋型剂灌胃,替勃龙组和雌激素组分别给予替勃龙和雌激素灌胃,于用药后50d处死全部动物,分别测定大鼠股骨的骨密度和骨组织形态计量参数。结果(1)骨密度(BMD)检测结果:模型组BMD低于假手术组(P<0.05),替勃龙组和雌激素组BMD高于模型组(P<0.05),替勃龙组BMD高于雌激素组(P<0.05)。(2)骨组织形态计量学分析结果:模型组骨小梁体积(TBV)、骨小梁表面(TBS)、纵向骨生长率(LBGR)、骨皮质矿化率(mAR)低于假手术组(P<0.05),骨小梁形成表面(TFS)、活性生成面(AFS)、骨小梁骨生成率(BFR)、骨小梁吸收表面(TRS)四项指标则高于假手术组(P<0.05);模型组TBV、TBS、LBGR、mAR低于替勃龙组和雌激素组(P<0.05);TFS、AFS、BFR、TRS则高于替勃龙组和雌激素组(P<0.05);替勃龙组TBV、TBS高于雌激素组(P<0.05);AFS、BFR、TRS低于雌激素组(P<0.05)。结论替勃龙治疗骨质疏松症疗效优于雌激素,明显改善去势大鼠骨小梁厚度,使骨小梁体积百分比增加,皮质骨平均厚度变厚,骨量增加。     

乳腺癌术后发生肝脏转移的相关危险因素分析

目的 研究损毁下丘脑弓状核对大鼠骨组织形态计量学的影响.方法 选用新生期SD雌性大鼠12只,随机分成2组:皮下注射10%谷氨酸单钠组(MSG实验组),同法注射等体积生理盐水组(NS对照组),各组大鼠皆存活至120d处死,取左侧胫骨上段制成不脱钙骨切片,行骨组织形态计量学研究.结果 与NS对照组相比,MSG实验组的骨小梁面积百分数(%Tb.Ar)降低23.21%(P<0.05),骨小梁宽度(Tb.Th)降低9.74%(P<0.05),骨小梁数量(Tb.N)减少14.65%(P<0.05),骨小梁分离度(Tb.Sp)升高24.04%(P<0.05).骨小梁荧光周长百分数(%L.Pm)降低32.89%(P<0.05),骨矿化沉积率(MAR)增加11.83%(P<0.05),骨形成率(BFR/TV、BFR/BV、BFR/BS)分别降低34.96%、16.91%、24.60%(P<0.05).骨小梁周长破骨细胞数量增加100%.结论 MSG损伤弓状核引起大鼠骨转换降低,骨形成减少,骨吸收增加,导致骨质疏松.     

XW630对去卵巢大鼠骨质疏松的作用(英文)

目的:研究XW630对去卵巢大鼠骨质疏松的影响。方法:血清E_2和骨钙素(BGP)浓度用放射免疫测定法。骨组织计量学用四环素内标法。结果:去卵巢后,血清E_2水平下降61.9％,子宫减轻72.7％,动情次数减少63.6％。XW630治疗13周后,血清BGP浓度增加75.7％,动情次数略增加,但低于假手术组,血清E_2浓度及子宫重量无明显变化。与OVX组相比,XW630组骨组织计量学指标TBV/TTV,TBV/SBV和MTPD增加;Sfract(s),Sfract(d),TOS和Svf增加,OMP缩短。结论:XW630增加骨激活频率、骨小梁连接性、稳定性和张力。表明XW630促进骨形成、抑制骨吸收,对生殖系统无影响。     

仙珠胶囊对去卵巢大鼠骨密度和血生化指标的影响

目的观察仙珠胶囊对去卵巢大鼠骨密度(BMD)、骨代谢标志物的影响。方法将去卵巢大鼠随机分为模型组,仙珠胶囊低、中、高剂量(2.715、5.430、10.860g生药/kg)组及阳性药倍美力片(0.104mg/kg)组。另设假手术组。连续ig给药3个月,测定血清中骨源性碱性磷酸酶(BALP)、Ⅰ型胶原交联羧基末端肽(CTX)、雌二醇(E2)、甲状旁腺素(PTH)、钙(Ca)、磷(P)的量,并剖取大鼠股骨测BMD。结果模型组大鼠BMD,E2、Ca、P的量低于假手术组(P<0.01);各给药组的这些指标高于模型组(P<0.05),高剂量仙珠胶囊组大鼠BMD高于阳性对照药(P<0.05)。模型组大鼠BALP、CTX、PTH高于假手术组(P<0.01),仙珠胶囊及倍美力组这3项指标均降低(P<0.01)。结论仙珠胶囊可有效增加去卵巢大鼠BMD,有效抑制骨丢失,增加成骨细胞活性,降低血清PTH水平,提高性激素水平。     

卵巢切除大鼠骨组织中细胞因子含量的改变及补肾中药对其的影响

目的观察卵巢切除大鼠骨组织中白细胞介素(IL)-1、IL-6和肿瘤坏死因子(TNF)-α的含量改变及补肾中药的调节作用。方法建立双侧卵巢切除(OVX)大鼠骨质疏松模型,去卵巢术后1周,用灌胃法给服补肾中药10周,以尼尔雌醇和生理盐水作为对照,观察各组大鼠骨密度及骨形态学的改变,并通过放射免疫法(RIA)检测各组大鼠骨组织中细胞因子IL-1β、IL-6和TNF-α的含量。结果①去势组较对照组骨密度显著下降(P<0.01),骨小梁稀疏断裂,骨组织中IL-1β、IL-6、TNF-α含量均显著增高(P<0.01)。②中药组骨密度显著高于去卵巢组(P<0.01),骨形态学亦显著改善。而骨组织中IL-1β、IL-6及TNF-α含量均显著低于去卵巢组(P<0.05)。结论去卵巢后大鼠骨组织中IL-1β、IL-6及TNF-α含量显著增加,而骨密度显著降低。补肾中药能较好地预防去卵巢所致大鼠的骨质疏松,其作用机制可能是其能有效地抑制去卵巢大鼠骨组织微环境中细胞因子IL-1β、IL-6和TNF-α的含量而减少骨丢失。     

三种小鼠骨质疏松模型骨组织形态计量学观察与评价

目的探讨D-半乳糖是否会引起骨质疏松,与去卵巢致骨质疏松有何异同,去卵巢后再加上D-半乳糖是否会加速加重骨质疏松的进展,补充雌激素是否有预防作用。方法 SPF级小鼠60只,随机分为假手术组、D-半乳糖组、去卵巢组、去卵巢+D-半乳糖组、去卵巢+D-半乳糖+己烯雌酚组和D-半乳糖+己烯雌酚组。实验70 d后,取右胫骨进行不脱钙骨组织切片及骨形态学计量学观察与评价。结果与假手术组比较,去卵巢组%Tb.Ar、Tb.Th、Tb.N明显降低(P<0.01),Tb.Sp明显升高(P<0.05),反映骨吸收指标的Oc.Pm、Oc.No.、%Oc.S、Oc.N/mm明显升高(P<0.01),反映骨形成指标的%L.Pm、MAR、BFR/TV、BFR/BV、BFR/BS明显降低(P<0.01)。D-半乳糖组反映骨吸收的4个指标明显升高(P<0.05),反映骨形成的4个指标明显降低(P<0.05)。去卵巢+D-半乳糖组也有明显的骨质疏松的表现,但各指标与去卵巢组相比,差异没有显著性,与D-半乳糖组相比,各指标差异也没有显著性。雌激素对D-半乳糖和去卵巢联合D-半乳糖导致的骨质疏松相关指标均有明显的对抗作用。结论去卵巢、D-半乳糖、去卵巢联合D-半乳糖均能建立小鼠骨质疏松模型,雌激素能有效防止D-半乳糖和去卵巢联合D-半乳糖致骨量丢失。     

大鼠去卵巢后对不同部位骨骼的影响

目的观察大鼠去卵巢90d后不同部位骨骼的变化特点。方法4.5月龄雌性SD大鼠20只,随机分为假手术组和去卵巢组,均灌喂5.6%乙醇5ml·kg-1·d-1,持续90d,用骨组织形态计量学方法测量胫骨上段和腰椎松质骨及胫骨中段皮质骨的动态和静态参数。结果去卵巢大鼠胫骨上段(PTM)和腰椎(LV)松质骨的骨量均减少,其中PTM骨量减少80.5%,LV骨量减少35.0%,胫骨中段(Tx)皮质骨的骨量未出现丢失,只是骨内、外膜的骨形成增加。结论大鼠去卵巢后呈现高转换型骨质疏松表现,不同部位的骨骼变化不同。     

前列腺素衍生物对去卵巢大鼠骨质疏松的治疗作用

目的观察前列腺素衍生物米索前列醇对去卵巢大鼠骨质疏松的治疗作用。方法10mon大鼠双侧卵巢去除,术后2mon开始用药物治疗,用药时间为2mon。用骨组织形态计量学方法测定大鼠第4腰椎松质骨静态、动态参数,大鼠第5腰椎体应用骨生物力学方法作椎体压缩试验。结果在去卵巢引起大鼠骨量降低的情况下,米索前列醇可使去卵巢大鼠骨小梁面积(%Tb.Ar)增加21.6%,但与去卵巢组相比,差异无统计学意义;米索前列醇可改善骨质疏松大鼠椎骨的生物力学状况,表现在能使去卵巢大鼠的破坏应力和弹性模量增加。结论前列腺素衍生物米索前列醇对去卵巢大鼠椎骨的生物力学状况有改善作用。     

骨金散对去卵巢大鼠Ⅰ型胶原交联N-端肽、Ⅰ型胶原mRNA表达的影响

目的：复制去卵巢大鼠骨质疏松动物模型,探讨中药骨金散对去卵巢雌性大鼠血清Ⅰ型胶原交联N-端肽（NTX）和骨组织Ⅰ型胶原mRNA表达的影响。方法：6月龄雌性SD大鼠40只,随机分为去势组和假手术组。去势组切除双侧卵巢,假手术组切除部分脂肪。大鼠去势后1个月,将去势组随机分为3组：模型组、雌激素组和骨金散组,雌激素组每日灌服己烯雌酚0.05m g/kg,骨金散组按1.8g/kg剂量灌服骨金散,其余各组灌服等量生理盐水。2个月后,酶联免疫吸附法测量血清碱性磷酸酶（ALP）、NTX水平,RT-PCR方法检测右侧股骨骨组织Ⅰ型胶原mRNA表达水平。结果：与假手术组比较,模型组血清ALP、NTX含量明显升高（P〈0.01）,Ⅰ型胶原mRNA水平显著下降（P〈0.01）。雌激素组和骨金散组大鼠体内的ALP、NTX水平显著低于模型组（P〈0.01）,骨金散组大鼠体内的ALP水平高于雌激素组（P〈0.05）。雌激素组和骨金散组实验大鼠骨组织中Ⅰ型胶原蛋白mRNA表达含量明显高于模型组（P〈0.01）。结论：骨金散可减轻去卵巢大鼠ALP、NTX水平的提高,上调骨组织Ⅰ型胶原mRNA的表达水平,这可能与其治疗骨质疏松的机制有关。     

Long-term effects of D-003, a mixture of high molecular weight acids from sugarcane wax, on bones of ovariectomized rats: a one year study

This study was done to determine the long-term effect of D-003 on bones of ovariectomized (ovx) rats distrib-uted in 4 groups: a false-operated and three groups of ovx rats: one treated with the vehicle and two with D-003 (5 and 250 mg/kg). D-003 significantly prevented, in a dose-dependent fashion, the trabecular bone volume (TBV), trabecular number (TbN) and trabecular thickness (TbTh) reduction induced in ovx rats and the increase of trabecular separation (TbSp) osteoclast number (OcN) and osteoclast surface (OcS/BS) increased in the positive controls versus the sham group. It is concluded that D-003 administered for 12 months prevented bone loss and decreased bone resorption in ovx rats, without evidences of impaired bone quality.     

Skeletal effects of parathyroid hormone (1-34) in ovariectomized rats with or without concurrent administration of salmon calcitonin

This study evaluated the effect of parathyroid hormone (PTH) infusion alone or in combination with salmon calcitonin (sCT) in ovariectomized (OVX) rats and compared it with daily PTH injections alone or in combination with sCT infusion. Female Sprague-Dawley rats were divided randomly into 6 groups and were either bilaterally ovariectomized or underwent a sham operation; they were then treated for 4 weeks, beginning the day after surgery. Each group of OVX rats received either PTH infusion (group 1), PTH + sCT infusion (group 2), sCT infusion + daily PTH injection (group 3), or daily PTH injection (group 4). One group each of OVX (group 5) and sham-operated rats (group 6) received daily injections of vehicle alone. PTH was injected at 80 microg/kg/day and infused at 40 microg/kg/day, whereas sCT was infused at 10 microg/kg/day. The animals were sacrificed 28 days after treatment, and cancellous bone volume was measured in the tibial metaphysis. Similar to daily PTH injections, continuous infusion of PTH alone increased cancellous bone volume significantly over that seen in vehicle-treated OVX and sham-operated rats. Although cancellous bone volume after continuous infusion of PTH + sCT was also significantly higher than that seen in vehicle-treated OVX and sham-operated rats, the increase was significantly lower than with the other 3 nonvehicle treatments. The increase in cancellous bone volume after administration of sCT infusion along with daily PTH injections was not different from that with daily PTH injections alone. Thus, at the doses tested, the beneficial effects of PTH injection were not apparently improved by PTH infusion or by combination with sCT.     

Effect of D-003, a mixture of very high molecular weight aliphatic acids, on prednisolone-induced osteoporosis in Sprague-Dawley rats

BACKGROUND: Drugs inhibiting cholesterol biosynthesis may affect bone metabolism through inhibition of the mevalonate pathway resulting in the inhibition of protein prenylation required for osteoclast activity. D-003 is a mixture of high molecular weight aliphatic primary acids purified from sugar-cane (Saccharum officinarum) wax, with cholesterol-lowering effects demonstrated in experimental and clinical studies. D-003 inhibits cholesterol biosynthesis through indirect regulation of HMG-CoA reductase activity. A previous study demonstrated that D-003 prevented bone loss and bone resorption on ovariectomy-induced osteoporosis in rats. Corticosteroid-induced osteoporosis is the result of changes affecting calcium homeostasis, but the hallmark of corticosteroid-induced bone loss is the direct effects on bone cells, such as inhibition of osteoblastogenesis, promotion of apoptosis of osteoblasts and osteocytes, and decrease in bone formation. OBJECTIVE: To determine whether D-003 could prevent the bone loss induced with prednisolone in Sprague-Dawley rats. METHODS: Rats were randomly distributed in five groups (ten rats per group): a sham-operated control and four groups orally treated with prednisolone 6 mg/kg for 80 days; a positive control orally treated with vehicle; and three groups orally treated with D-003 at 5, 25 and 200 mg/kg, respectively. Rats were killed, bones removed and histological variables of bone resorption and formation studied for histomorphometry. RESULTS: Compared with the sham group, prednisolone significantly (p < 0.01) reduced trabecular bone volume (TBV), while D-003 significantly (p < 0.001) and dose-dependently prevented the prednisolone-induced reduction of TBV. Treatment with prednisolone lowered (p < 0.001) trabecular thickness (TbTh) and number (TbN), while increasing (p < 0.001) the gap between trabeculae. D-003 (5, 25 and 200 mg/kg/day) significantly (p < 0.001) and dose-dependently prevented the reduction of TbTh and TbN and the increase of trabecular gap induced with prednisolone. Treatment with prednisolone increased both the surface and number of osteoclasts compared with sham (p < 0.001). D-003 (5-200 mg/day), however, prevented this effect (p < 0.001 for all comparisons). D-003 also prevented (p < 0.001) the reduction of osteoblast surface (ObS/BS) induced by prednisolone. Osteonecrotic areas were observed in all positive controls, but in none of the sham animals. Positive controls showed hypertrophy of bone marrow adipocytes and lipid-laden pluripotential stromal cells in bones. A significant and dose-dependent reduction of the frequency of animals showing prednisolone-induced osteo-necrosis was observed across the doses of D-003 (5, 25 and 200 mg/kg) investigated here. CONCLUSIONS: D-003 (5, 25 and 200 mg/kg) prevented trabecular bone loss and femoral neck osteonecrosis induced with prednisolone in Sprague Dawley rats, also increasing osteoblast surface and reducing bone resorption parameters. These results suggest that D-003 could be useful for managing corticosteroid-induced osteoporosis.     

Skeletal effects of parathyroid hormone (1–34) in ovariectomized rats with or without concurrent administration of salmon calcitonin

This study evaluated the effect of parathyroid hormone (PTH) infusion alone or in combination with salmon calcitonin (sCT) in ovariectomized (OVX) rats and compared it with daily PTH injections alone or in combination with sCT infusion. Female Sprague-Dawley rats were divided randomly into 6 groups and were either bilaterally ovariectomized or underwent a sham operation; they were then treated for 4 weeks, beginning the day after surgery. Each group of OVX rats received either PTH infusion (group 1), PTH+sCT infusion (group 2), sCT infusion+daily PTH injection (group 3), or daily PTH injection (group 4). One group each of OVX (group 5) and sham-operated rats (group 6) received daily injections of vehicle alone. PTH was injected at 80 μg/kg/day and infused at 40 μg/kg/day, whereas sCT was infused at 10 μg/kg/day. The animals were sacrificed 28 days after treatment, and cancellous bone volume was measured in the tibial metaphysis. Similar to daily PTH injections, continuous infusion of PTH alone increased cancellous bone volume significantly over that seen in vehicle-treated OVX and sham-operated rats. Although cancellous bone volume after continuous infusion of PTH+sCT was also significantly higher than that seen in vehicle-treated OVX and sham-operated rats, the increase was significantly lower than with the other 3 nonvehicle treatments. The increase in cancellous bone volume after administration of sCT infusion along with daily PTH injections was not different from that with daily PTH injections alone. Thus, at the doses tested, the beneficial effects of PTH injection were not apparently improved by PTH infusion or by combination with sCT.     

异普黄酮抗卵巢切除大鼠的骨质疏松与上调腰椎护骨素mRNA的表达

目的：制造绝经后骨质疏松（postamenopausal osteopomsis，PMOP）的大鼠动物模型，研究异普黄酮（Ipriflavone，Ip）对卵巢切除大鼠腰椎护骨素（OPG）基因mRNA表达水平的影响，探讨其预防和治疗PMOP的作用机制。方法：6月龄未交配健康雌性Sprague-Dawley大鼠4JD只，随机分为假手术组（Sham），卵巢切除组（OVX），OVX＋戊酸雌二醇组（E2）和OVX＋Ip组（Ip）。灌胃13周后处死动物，第四腰椎行骨组织形态计量指标测定，第二腰椎采用RT—PCR方法，对OPGmRNA表达水平进行检测。结果：OVX组大鼠较假手术组骨小梁体积百分比（TBV％）显著下降；类骨质体积百分比（OSV％）明显升高（P〈0．05）；E2和Ip均可使OVX大鼠的TBV％明显升高，OSV％明显下降；OPG mRNA表达水平在OVX大鼠骨组织中下调，与假手术组相比有显著性差异（P〈0．05），E2和IP均可上调OVX大鼠骨组织OPG mRNA表达水平（P〈0．05）。结论：实验成功制造了大鼠PMOP模型；E2和Ip均通过抑制骨转换发挥预防和治疗PMOP的作用；PMOP的发生与OPG有关，Ip和E2一样，其预防和治疗骨吸收效应很可能是通过OPG介导的。     

甲状旁腺激素1-34促进尾悬吊再负重大鼠骨质量恢复

以往研究中已经证实甲状旁腺激素1-34（PTH1-34）抗骨质疏松效果,然而PTH1-34对于拟失重再负重大鼠骨量的恢复是否有促进作用尚未见报道。目的：观察尾悬吊大鼠再负重骨量的变化及PTH1-34干预对该过程的影响及机制。方法：5月龄大鼠24只分为4组,每组6只：对照组（Control组）、尾悬吊（Unloading）4周组（Unloading）, UL组）、尾悬吊2周再负重（Reloading）2周组（UL+RL组）、尾悬吊2周再负重加PTH1-34干预2周组（20ug/kg/d, 5 days/week, UL+RL+PTH组）;4周后处死大鼠,分离左侧胫骨制备硬组织切片,行骨组织形态计量学分析;检测左侧股骨骨密度;取右侧胫骨制备组织匀浆,提取蛋白和RNA,分别采用Western blot和Realtime PCR检测骨钙素（OCN）的表达;三点弯曲试验分析右侧股骨最大载荷和弹性模量。结果：1、骨密度：CL组显著高于其余三组（P < 0.05）,UL+RL组和UL+RL+PTH组均显著高于UL组（P < 0.05）;UL+RL+PTH组显著高于UL+RL组（P <0.05）; 2、骨组织形态计量学：BV/TV：CL组显著高于UL、UL+RL、UL+RL+PTH组（P < 0.05）,UL组显著低于UL+RL组和UL+RL+PTH组（P < 0.05）;UL+RL+PTH组显著高于UL+RL组（P <0.05）;Tb.N：CL组显著高于其余三组（P < 0.05）,UL+RL+PTH组显著高于UL组（P < 0.05）;Tb.Th：任意两组间比较,差异无统计学意义（P >0.05）;Tb.Sp：CL组显著低于UL、UL+RL、UL+RL+PTH（P < 0.05）,UL组显著低于UL+RL组和UL+RL+PTH组（P < 0.05）; 3、生物力学分析结果：最大载荷：UL组显著低于其余三组,UL+RL组显著低于CL组（P < 0.05）;弹性模量：CL组显著高于其余三组（P < 0.05）,UL+RL+PTH组显著高于UL组、UL+RL组（P < 0.05）;4、Western blot： OCN蛋白表达在CL组和UL+RL+PTH组显著高于UL组（P < 0.05）;5、Realtime PCR检测结果：各组间的mRNA表达水平无显著差别。结论：尾悬吊2周可诱发大鼠下肢骨量丢失、力学性能下降、OCN含量减少,再负重2周后上述改变可得到部分恢复,PTH1-34干预能促进这一过程。     

氟化钠和尼尔雌醇联合应用对去卵巢大鼠胫骨作用的研究

目的：了解卵巢切除（ＯＶＸ）大鼠胫骨对氟化钠和尼尔雌醇联合应用的治疗反应。方法：将２４只雌性大鼠随机分成３组：ＯＶＸ组，对照组和ＥＦ组，每组８只。对ＯＶＸ组和ＥＦ组大鼠行ＯＶＸ手术，建立骨质疏松动物模型。ＥＦ组于ＯＶＸ术后１个月予氟化钠和尼尔雌醇联合治疗，给药３个月后处死。用骨形态计量学方法检测ＯＶＸ大鼠左后肢胫骨对氟化钠的治疗反应。结果ＯＶＸ组大鼠骨小梁体积，平均骨小梁密度较对照组显著减少；