益肾健骨膏对去卵巢骨质疏松大鼠骨代谢的影响

目的 探讨益肾健骨膏对去卵巢骨质疏松大鼠骨代谢的影响及可能机制。方法 50只雌性SD大鼠被随机分为假手术组、模型组、高剂量膏方组、低剂量膏方组、阳性药物组,每组10只。假手术组、模型组给予10 mL /（kg·d）生理盐水灌胃,低、高剂量膏方组分别给予2 g /（kg·d）、13 g/（kg·d）益肾健骨膏灌胃,阳性药物组灌服6.25 mg/（kg·w）阿仑膦酸钠维D3。治疗12周后检测大鼠腰椎骨密度和腰椎最大压缩载荷,通过Elisa检测血清骨代谢指标抗酒石酸酸性磷酸酶（TRACP）、骨保护素(OPG)、Ⅰ型前胶原氨基端原肽(PINP)、Ⅰ型胶原交联羧基端肽(CTX-Ⅰ),RT-PCR检测腰椎骨组织OPG、RANKL、RANK、TRAF6的 mRNA表达,RT-PCR及Western blot检测腰椎Notch1、Notch2、Jagged1、Jagged2的基因及蛋白表达。结果 益肾健骨膏治疗12周后,与模型组比较,高剂量膏方组大鼠腰椎骨密度、最大压缩载荷,血清PINP、OPG水平,骨组织Notch1、Notch2、Jagged1、Jagged2的mRNA和蛋白表达,OPG的mRNA表达显著升高（P<0.05）,而血清TRACP、CTX-Ⅰ水平,骨组织RANKL、RANK、TRAF6的mRNA表达显著降低（P<0.05）。结论 高剂量益肾健骨膏能改善去卵巢骨质疏松大鼠骨密度、骨强度及骨代谢,其作用机制可能与Notch通路及OPG/RANKL/RANK系统有关。     

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。     

老鹳草素对地塞米松诱发大鼠骨质疏松症的影响

目的 观察老鹳草素对地塞米松诱发大鼠骨质疏松症的影响.方法 将6个月龄雌性Wistar大鼠随机分为对照组、模型组、5、10、20 mg/kg老鹳草素组和2 mg/kg阿仑膦酸钠组.大鼠肌肉注射地塞米松(1 mg/kg),老鹳草素连续灌胃90d,对股骨和腰椎进行骨密度及骨组织形态计量学检测.结果 对照组股骨和椎骨骨密度分别为(0.20±0.01)和(0.18±0.01) g/cm2,模型组分别为(0.15±0.01)和(0.10 ±0.01) g/cm2,差异有统计学意义(P＜0.05).与模型组比较,10、20 mg/kg老鹳草素能显著提高股骨和椎骨的骨密度.5 mg/kg老鹳草素可增加模型组大鼠股骨骨小梁表面积百分率、骨小梁间距和骨小梁节点数;10、20 mg/kg老鹳草素明显增加模型组大鼠股骨和椎骨骨小梁计数、骨小梁宽度和骨小梁表面积百分率,增多小梁节点数、减少骨小梁间隙距离和小梁游离末端数.结论老鹳草素具有抑制地塞米松引起大鼠骨质疏松症的作用,并呈剂量-效应关系.     

血管紧张素Ⅱ受体抑制剂对去卵巢骨质疏松小鼠腰椎骨组织的影响及可能机制

目的探讨血管紧张素Ⅱ受体抑制剂对去卵巢骨质疏松小鼠腰椎骨组织的影响及可能的机制。方法将60只雌性小鼠随机平均分为假手术组、模型组和氯沙坦治疗组,模型组和氯沙坦治疗组均将小鼠双侧卵巢切除建立骨质疏松模型。术后第7天开始,假手术组和模型组小鼠每天灌服0.5 m L生理盐水,氯沙坦治疗组小鼠按照10 mg/(kg·d)的剂量灌服氯沙坦水溶液0.5 m L。建模后8周和12周时,检测各组小鼠血清中雌二醇、碱性磷酸酶(ALP)、骨钙蛋白(OCN)和Ⅰ型前胶原羧基端前肽(PICP)水平,采用Micro-CT三维成像系统对小鼠腰椎进行骨形态计量学检测,采用实时荧光定量PCR技术检测各组小鼠腰椎组织中骨保护素(OPG)、核因子κB受体活化因子(RANK)和核因子κB受体活化因子配体(RANKL)表达。结果与假手术组相比,模型组和氯沙坦治疗组小鼠8周、12周时血清雌二醇水平均降低;模型组小鼠8周、12周时血清ALP、OCN和PICP水平均升高;氯沙坦治疗组小鼠8周时血清ALP、OCN和PICP水平均升高;差异均有统计学意义(P0.05)。与模型组比较,氯沙坦治疗组8周、12周时小鼠血清ALP、OCN和PICP水平差异均降低,差异有统计学意义(P0.05)。与8周时相比,模型组12周时血清ALP、OCN和PICP水平均升高,氯沙坦治疗组12周时血清ALP、OCN和PICP水平均降低,差异均有统计学意义(P0.05)。与假手术组相比,模型组和氯沙坦治疗组骨密度(BMD)、骨小梁数量(Tb.N)、骨小梁体积分数(BV/TV)和骨小梁厚度(Tb.Th)均降低,而骨小梁间隙(Tb.Sp)和结构模型指数(SMI)均升高,差异均有统计学意义(P0.05);与模型组相比,氯沙坦治疗组BMD、Tb.N、BV/TV和Tb.Th均升高,而Tb.Sp和SMI均降低,差异均有统计学意义(P0.05)。与假手术组相比,模型组和氯沙坦治疗组小鼠腰椎组织中OPG m RNA、RANK m RNA相对表达量均降低,而RANKL m RNA相对表达量和RANKL/OPG比值均升高,差异均有统计学意义(P0.05);与模型组相比,氯沙坦治疗组小鼠腰椎组织中OPG m RNA、RANK m RNA相对表达量均升高,而RANKL m RNA相对表达量和RANKL/OPG比值均降低,差异均有统计学意义(P0.05)。结论血管紧张素Ⅱ受体抑制剂可能通过促进骨形成、抑制骨吸收,减少负转换而导致的骨丢失,从而改善去卵巢骨质疏松小鼠腰椎骨组织骨质疏松状态。     

淫羊藿总黄酮对摘除卵巢大鼠骨质疏松症的防治作用

用除卵巢法结合低钙饲料建立大鼠骨质疏松模型。淫羊藿总黄酮在75-300mg/kg剂量范围内连续给药3个月，与模型组大鼠比较，能明显提高大鼠股骨表现观面密度（W/LD）和骨密度（BMD）而不升高子宫系数及血清雌二醇（s-E2)水平，并有提高骨Ca、骨P的趋势。高剂量组大鼠血清碱性磷酸酶（s-ALP)降低，股骨骨密度升高。骨形态计量学结果表明，高剂量组大鼠骨小梁吸收表面百分率（TRS%）和形成表面百分率（TFS%）等参数明显降低，骨小梁体积百分率（TBV%）明显提高。     

辛伐他汀对去卵巢大鼠脊椎椎体骨形成功能影响的实验研究

目的 观察辛伐他汀对去卵巢大鼠腰椎椎体骨形成功能的影响,评价辛伐他汀对躯干骨骼的骨质疏松是否具有预防和治疗作用。方法 6月龄雌性SD大鼠60只,每组10只,50只切除双侧卵巢分为剂量组和对照组,另10只作为假手术平行对照组。以不同剂量辛伐他汀（5mg、10mg 、20mg 及40mg /kg/d）灌胃。三个月后分别行腰4椎体的双能X线骨密度测试,周围定量CT（pQCT）纵向扫描和腰5椎体的生物力学压缩测试。结果 （1）骨密度和pQCT扫描值：10mg、20mg剂量组数值较高,但皆无统计学差异。（2）生物力学测试：10mg、40mg剂量组数值较高,但无统计学差异。结论 辛伐他汀10mg/kg/d灌胃组（相当人体口服辛伐他汀12 mg～24mg/天）在多数指标中好于其它剂量组,但未发现明显统计学差异。说明辛伐他汀对去卵巢大鼠的躯干骨骼并不具有明显的骨形成促进作用,即对脊柱椎体的骨质疏松并不具有预防和治疗的作用。     

银杏叶提取物不同给药方式对骨质疏松大鼠成骨的影响

目的探讨银杏叶提取物(Ginkgo Biloba Extract,GBE)不同体内给药方式对骨质疏松(Osteoporosis,OP)大鼠成骨的影响。方法构建去势大鼠骨质疏松模型(osteoporosis in ovariectomized rats,OVX)64只和糖皮质激素性骨质疏松大鼠模型(Glucococticoid-induced osteoporosis in rats,GIOP)64只。并将两组骨质疏松大鼠用随机数字表法分为3组不同浓度灌胃给药(100 mg/(kg·d)、200 mg(kg·d)、400 mg(kg·d)和3组注射给药(3.5 mg/(kg·d)、4.0 mg/(kg·d)、4.5 mg/(kg·d)),设立模型对照组2组,空白对照组1组(每组8只)。采用ELISA染色法检测血清骨钙素(OC)、抗酒石酸酸性磷酸酶(TRAP),观察股骨横切HE染色病理改变。结果与对照组相比,两组大鼠构模2个月后,OC、TRAP水平检测,大鼠股骨远端横断观察,符合骨质疏松改变。两组骨质疏松模型通过不同方式和浓度的给药后,与不给药对照组相比,OC水平上升(P0.01),TRAP水平下降(P0.05)。组织学观察可见,两组大鼠给药后均有不同程度新生骨小梁形成,骨小梁排列整齐,有不同程度的变粗,数量增多。结论 GBE灌胃给药与腹腔注射给药对骨质疏松大鼠的成骨均有促进作用,促进成骨细胞分泌OC,抑制破骨细胞的分泌TRAP,可以促进骨小梁的形成,增强骨的致密度,作用效果与给药方式和剂量有直接关系。     

不同剂量普萘洛尔对去卵巢大鼠骨密度和生化指标的影响

目的 观察盐酸普萘洛尔片对于去卵巢大鼠骨密度（BMD）、骨代谢标志物的影响。方法 将60大鼠随机分组：假手术组,模型空白组（生理盐水）,高剂量组[20mg/（kg.d）],中等剂量组[5mg/(kg.d）],低剂量组[1mg(/kg.d）]。假手术组在卵巢附近切除等量脂肪组织,其余各组行双侧卵巢摘除手术,术后3个月后,检测骨密度,之后,假手术组和模型空白组给予生理盐水,其余根据剂量不同每日给予大鼠灌胃相应剂量普萘洛尔水溶液。分别于第4周和第8周,检测各组BMD及骨代谢生化指标。结果 假手术组均高于各组（P＜0.01）,低剂量和中等剂量组高于高剂量组和生理盐水组（P＜0.05）,高剂量组与生理盐水组无统计学差异（P＞0.05）。结论 低剂量的普萘洛尔对于骨质疏松大鼠模型,可抑制骨量丢失,增加成骨细胞活性。高剂量的普萘洛尔对于骨量调节不明显。     

橙皮苷对去卵巢骨质疏松症大鼠骨质流失和机制的影响

目的研究橙皮苷对去卵巢骨质疏松大鼠骨质流失和骨保护素(osteoprotegerin,OPG)/核因子kappa B配体的受体激活物(receptor activator of nuclear factor kappa B ligand,RANKL)/RANK通路的影响。方法将48只雌性Sprague-Dawley(SD)大鼠随机分为假手术组、去卵巢骨质疏松组、橙皮苷低剂量组、橙皮苷中剂量、橙皮苷高剂量组和雌激素组。检测骨组织骨体积分数(bone volume fraction,BV/TV)、骨小梁厚度(trabecular thickness,Tb.Th)、骨密度(bone mineral density,BMD)、骨小梁数量(trabecular number,Tb.N)、骨小梁分离度(trabecular separation,Tb.Sp),通过HE染色观察骨组织病理损伤,采用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测人Ⅰ型胶原C端肽(C-terminal peptide collagen typeⅠ,CTX-Ⅰ)和血清骨钙素(bone glaprotein,BGP)的表达量。运用qRT-PCR和Western bolt分别检测骨组织OPG、RANKL、RANK的mRNA和蛋白表达。结果在橙皮苷治疗后,与去卵巢骨质疏松组相比,骨质疏松标志物BV/TV、BMD、Tb.Th和Tb.N水平升高,Tb.Sp水平降低;大鼠骨小梁数量明显增加,且骨小梁连接更为紧密;骨吸收标志物CTX-Ⅰ水平降低;骨形成标志物BGP水平升高。OPG mRNA相对表达量和蛋白的表达量升高,RANKL和RANK mRNA相对表达量和蛋白的表达量降低。结论橙皮苷能缓解去卵巢骨质疏松大鼠骨质流失并调节OPG/RANKL/RANK信号通路。     

川牛膝在去卵巢大鼠体内的骨保护作用

目的 观察川牛膝在去卵巢大鼠体内的抗骨质疏松作用。方法 3月龄雌性SD大鼠50只随机分为5组:假手术组 (SHAM)、单纯去卵巢组（OVX)、己烯雌酚组（ERT组,22.5μg/kg? d,ig)、高剂量川牛膝组（CH,14 g/kg? d,ig)、低剂量川牛膝 组(CL,7 g/kg? d,ig)。其中,40只大鼠切除双侧卵巢,SHAM组仅切除卵巢周围等量脂肪组织,术后第8天开始给药,给药12 周后处死所有大鼠,测定腰椎骨密度（L-BMD)、股骨骨密度（F-BMD)及骨生物力学性能：弹性模量（ELASTIC)、刚度 (STIFFNESS)、最大应力（M-STRESS)及最大承载力（M-LORD),并测定血清钙（Ca)、磷（P)、碱性磷酸酶(ALP)、尿羟脯氨酸 (HOP )、肌酐(Cr)值。结果 高剂量川牛膝组及己烯雌酚组大鼠腰椎和股骨的骨密度及骨生物力学性能均高于OVX组（P <0. 05),而尿羟脯氨酸/肌酐值及血清Ca、P含量低于OVX组（P <0.05)。结论 川牛膝在去卵巢大鼠体内能抑制骨量丢失、改善骨生物力学性能,预防骨质疏松的发生。     

墨旱莲对维甲酸所致大鼠骨质疏松症的药效学研究

目的探讨中药墨旱莲对维甲酸所致大鼠骨质疏松症的药效作用。方法 3月龄SPF级雌性SD大鼠60只,随机分为正常对照组、模型组(RA,75 mg/(kg·d))、墨旱莲组(1.46、0.73、0.37 g/(kg·d))、仙灵骨葆组(1.5 g/(kg·d))。除正常组外,其余各组给予维甲酸造模2 w,造模同时给予墨旱莲、仙灵骨葆。实验过程每日称量体重,连续给药6w后测定血钙(S-Ca)、血磷(S-P)、血清中碱性磷酸酶(ALP)和骨钙素(OCN)的水平,尿液中钙(U-Ca)、磷(U-P)、脱氧吡啶啉(DPD)的水平。采用DXA型骨密度仪检测大鼠的股骨、第4椎骨、胫骨的骨密度(bone mineral density,BMD)。三点弯曲试验检测左侧股骨生物力学性能:最大载荷、结构硬度、能量吸收、最大应力、弹性模量。Micro CT法分析右侧股骨骨微结构。结果墨旱莲1.46 g/(kg·d)能显著升高模型组大鼠的血钙水平,同时降低尿钙、ALP、OCN和DPD(P0.05)水平。与模型组相比,墨旱莲1.46 g/(kg·d)对维甲酸所致骨质疏松大鼠的股骨、第四椎骨及胫骨骨密度分别提高8.17%、11.79%、14.59%(P0.05),对最大载荷、结构硬度、能量吸收、最大应力、弹性模量等生物力学参数分别提高13.98%、16.33%、40.18%、12.45%、34.96%(P0.05),同时能有效抑制维甲酸所致大鼠股骨干骺端骨小梁微结构的退化(P0.05)。结论墨旱莲1.46 g/(kg·d)对维甲酸所致大鼠的骨质疏松症有防治作用,其作用机制可能与增强钙吸收、促进成骨细胞活性、降低骨转换率有关。     

二甲双胍对SD大鼠骨密度和体成分作用的研究

目的观察不同剂量二甲双胍作用不同时间对SD大鼠骨密度和体成分的影响。方法60只3月龄SD大鼠按随机数字法分为对照组和二甲双胍100 mg/(kg·d)组、200 mg/(kg·d)组、300 mg/(kg·d)组、500 mg/(kg·d)组。每组12只。每日灌胃1次。分别于干预前,干预后4周、8周、12周测定大鼠全身骨密度及体成分。结果干预8周和12周,不同剂量二甲双胍组骨密度均高于对照组(P<0.05)。干预8周,不同剂量二甲双胍组骨密度均高于4周组(P<0.05);干预12周,二甲双胍200 mg/(kg·d)组和300 mg/(kg·d)组骨密度均高于8周组(P<0.01)。干预12周,不同剂量二甲双胍干预组体重均低于对照组(P<0.01),二甲双胍500 mg/(kg·d)组体重低于100 mg/(kg·d)组和200 mg/(kg·d)组(P<0.05)。干预8周,不同剂量二甲双胍组脂肪含量均低于对照组(P<0.05);干预12周,不同剂量二甲双胍组脂肪含量均低于对照组(P<0.05),二甲双胍300 mg/(kg·d)组脂肪含量低于100 mg/(kg·d)组和200 mg/(kg·d)组(P<0.01),二甲双胍300 mg/(kg·d)组和500 mg/(kg·d)组脂肪含量均低于8周组(P<0.05)。干预12周,二甲双胍200 mg/(kg·d)组和300 mg/(kg·d)组肌肉含量均高于对照组(P<0.05)。结论二甲双胍可增加SD大鼠的骨密度和肌肉含量,减少脂肪含量和减轻体重,与干预时间和剂量有关。     

Prevention of disuse osteoporosis in rats by Cordyceps sinensis extract

Summary

Cordyceps sinensis has been known as a traditional medicine in China, and C. sinensis plus strontium could prevent osteoporosis in ovariectomized rats. The present study shows that daily oral administration of C. sinensis at higher doses in adult hind limb suspension rats can prevent disuse-induced bone loss and deterioration of trabecular microarchitecture.

Introduction

Cordyceps sinensis induces estradiol production and prevents osteoporosis in ovariectomized rats. This study was to examine whether C. sinensis can prevent disuse-induced osteoporosis.

Methods

Rats were randomly divided into six groups, and five groups were treated with hind limb suspension (HLS). One HLS group received alendronate (2.0?mg/kg/day) orally, and to the three other HLS groups to each group, a different amount of C. sinensis (100, 300, and 500?mg/kg/day) was orally administered for 8?weeks before and after HLS. The remaining HLS group was set as a control without treatment. Each group consisted of 10 males and females. The body weights, biochemical parameters in serum and urine, bone mineral density (BMD), bone mineral content (BMC), mechanical testing, and bone microarchitecture were examined.

Results

Treatments with higher C. sinensis dosage (300 and 500?mg/kg/day) or alendronate had a positive effect on body weights, mechanical strength, BMD, and BMC compared to the other HLS groups. C. sinensis decreased markers of bone turnover dose dependently and increased the osteocalcin levels in HLS rats. The result of micro-CT analysis from the L4 vertebra showed that C. sinensis (500?mg/kg) significantly prevented the reduction of the bone volume fraction, connectivity density, trabeculae number, and thickness as well as improved the trabeculae separation and structure model index in HLS rats.

Conclusions

The present study demonstrates that administration of C. sinensis at higher doses over an 8-week period can prevent the disuse osteoporosis in rats. It implies that C. sinensis might be an alternative therapy for prevention of disuse-induced osteoporosis also in humans.     

大黄素治疗对去卵巢大鼠骨量流失的保护作用机制研究

目的探讨大黄素(emodin,DHS)对去卵巢大鼠骨量流失的影响,并探索可能的机制。方法通过双侧去卵巢建立骨质疏松大鼠模型;随后随机分为假手术组(Sham)、去卵巢组(OVX)以及大黄素组(DHS),每组10只;其中DHS组大鼠接受大黄素[90 mg/(kg·d)]治疗12周;待治疗结束后使用Micro-CT、HE染色切片、骨代谢指标、以及蛋白质印迹观察治疗效果以及可能的机制。结果治疗12周后,与OVX组相比,Micro-CT和HE染色切片结果显示DHS组的大鼠骨小梁数量和骨密度得到明显改善。DHS组大鼠BMD、TV/BV、Tb.N、Tb.Th和Tb.Sp较OVX组明显改善(P<0.05)。与OVX组相比,DHS组的BALP水平明显升高(P<0.05);而TRACP-5b和β-CTX水平显著降低(P<0.05)。和OVX组比较,DHS组OPG表达水平上调(P<0.05),而RANKL和β2AR表达水平下调(P<0.05)。结论大黄素可以通过降低β2AR表达和激活OPG/RANKL信号通路介导对去卵巢大鼠骨量流失的保护作用。     

Co-treatment of PTH with osteoprotegerin or alendronate increases its anabolic effect on the skeleton of oophorectomized mice.

We examined the effects of 60 days of co-treatment of PTH with either OPG or alendronate in oophorectomized mice. Compared with PTH alone, co-treatment of PTH with either of these two mechanistically distinct anti-catabolics improved bone volume, mechanical strength, and appendicular and axial mineralization and prolonged the beneficial effect of PTH on BMD. INTRODUCTION: Conflicting evidence exists as to whether the anabolic effect of PTH is inhibited by the action of anti-catabolics. To examine this issue, we assessed the effects of alendronate and osteoprotegerin (OPG), two anti-catabolics with different modes of action, on the anabolic activity of PTH(1-34) in the skeleton of 4-month-old oophorectomized mice. MATERIALS AND METHODS: Mice treated with vehicle alone (PBS), alendronate alone (100 microg/kg/week), OPG alone (10 mg/kg twice a week), or PTH alone (80 microg/kg/day) were compared with each other and with animals administered PTH plus alendronate or PTH plus OPG. We assessed lumbar spine and femoral BMD at 0, 30, and 60 days. Contact radiography, histology, and histomorphometry, three-point bending assay of the femur, and serum osteocalcin and TRACP5b assays were performed at 2 months. RESULTS: Although alendronate and OPG each suppressed bone turnover, at the doses used, this was more profound with OPG. Increases in lumbar spine and femoral BMD and in trabecular bone volume were at least as great with OPG as with alendronate, and mechanical indices of femoral bone strength improved only with OPG. Both produced a plateau in spine and femoral BMD increases by 30 days. Co-treatment of PTH with each anti-catabolic produced additive increases in BMD in the femur and supra-additive increases in the lumbar spine with no plateau effects. Neither anti-catabolic impeded the PTH-induced increase in bone volume or the increase in mechanical strength of the femur. CONCLUSIONS: These studies show that the highly potent anti-catabolic OPG can produce dramatic increases in BMD and bone strength; that the temporal pattern of activity of bone formation and resorption modulators may have major influence on net skeletal accrual; and that, depending on timing, inhibition of osteoclastic activity may markedly augment the anabolic action of PTH.     

蛇床子素对绝经后骨质疏松症大鼠骨代谢的调节作用及机制

目的 探究蛇床子素对绝经后骨质疏松症(postmenopausal osteoporosis,PMO)模型大鼠骨代谢生化指标及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)通路的影响.方法 选取90只雌性大鼠,采用随机数字表法将大鼠分为:健康对照组、模型组、雌二醇组和蛇床子素低、中、高剂量组,每组15只.除健康对照...     

Effects of nicotine on bone mass and strength in aged female rats.

This study investigated the effects of nicotine on bone mass and biomechanical properties in aged, estrogen-replete (sham-operated) and estrogen-deplete (ovariectomized) female rats. Eight month old, retired breeder, sham-operated and ovariectomized Sprague-Dawley rats were left untreated for 12 weeks to establish cancellous osteopenia in the ovariectomized group. The animals were then administered saline, low dose nicotine (6.0 mg/kg/day) or high dose nicotine (9.0 mg/kg/day) via osmotic minipumps for 12 weeks. Vertebrae and femora were collected at necropsy for determination of bone mass and strength. As expected, ovariectomy had a negative effect on most endpoints evaluated. Vertebral body bone mineral content (BMC) and density (BMD) and the structural (ultimate load and yield load) and material (ultimate stress, yield stress, and flexural modulus of elasticity) strength properties were lower in the OVX rats than in the sham-operated rats. Femoral diaphysis BMC, BMD, ultimate load, and flexural modulus were also lower in the OVX rats than in the sham-operated rats. The nicotine doses administered resulted in serum nicotine levels that averaged 1.5-4.5-fold greater than those observed in heavy smokers. Despite the high doses used, nicotine had no effect on vertebral BMC, BMD, or any of the structural and material strength properties in either the OVX or the Sham rats. In addition, nicotine had no effect on femoral diaphysis BMC, BMD, ultimate load, stiffness, ultimate stress, or flexural modulus. Femoral yield load and stress were lower in low dose nicotine-treated rats than in vehicle-treated rats. However, differences were not detected between the high dose nicotine- and vehicle-treated rats for either femoral yield load or stress. The results suggest that tobacco agents other than nicotine are responsible for the decreased bone density and increased fracture risk as observed in smokers.     

依替二膦酸锶对大鼠腰椎及股骨骨密度的影响

目的观察新合成的抗骨质疏松化合物依替二膦酸锶对骨代谢的影响。方法以去势SD大鼠为基础,对依替二膦酸锶、依替二膦酸二钠和二氯化锶以及不同剂量依替二膦酸锶对大鼠股骨及腰椎的骨密度的影响进行动态观察和比较。结果依替二膦酸锶与相同摩尔剂量的依替二膦酸二钠和二氯化锶相比,对去势大鼠腰椎和股骨骨密度的影响更为明显。其干预后去势大鼠骨密度增加的出现更早,且其升高的幅度也较高。50 mg/(kg·d)、100 mg/(kg·d)和150 mg/(kg·d)3种不同剂量的依替二膦酸锶均能有效地增加去势大鼠椎体和股骨的骨密度,且其增加骨密度的能力无明显差异。结论新化合物中的骨吸收抑制物依替二膦酸和骨形成促进物锶进入大鼠体内后,两者的生物学效应可能存在互补性。     

白藜芦醇抗切除卵巢大鼠发生骨质疏松的作用研究

目的研究白藜芦醇(resveratrol,R)抗切除卵巢大鼠发生骨质疏松的作用。方法 6月龄Wistar雌性大鼠40只,随机数字表法分为假手术组(Sham)、去卵巢组(OVX)、淫羊藿苷组(I)和白藜芦醇组(R)。I组给予25 mg/(kg·d)的淫羊藿苷灌胃,R组给予8.4 mg/(kg·d)的白藜芦醇灌胃,Sham和OVX组灌胃等体积蒸馏水。根据体质量每两周进行一次灌胃剂量调整。8周后待各组间骨密度出现显著性差异后立即处死,统计大鼠体质量并计算大鼠器官指数,检测离体骨密度、骨生物力学、血清生化指标,观察骨组织形态并测量分析骨小梁相关静态参数。结果各组大鼠体质量并未出现统计学差异,除子宫系数外其他器官指数无统计学差异(P0.05),但OVX组的子宫指数显著低于Sham组(P0.05),I组和R组子宫指数显著高于OVX组(P0.05);与OVX组相比,I组和R组的骨密度、最大载荷、弹性模量、骨形成指标OC以及Tb.N、BV/TV均显著升高(P0.05),而骨吸收指标TRACP-5b含量和Tb.SP均显著降低(P0.01);骨组织形态观察结果也显示I组和R组骨小梁网状结构呈致密性增加,骨小梁数目明显变多。R组与I组相比,其各指标平均值略低于I组,差异均无统计学意义(P0.05)。结论白藜芦醇可能通过增加骨密度、提高骨强度、促进骨形成、抑制骨吸收、改善骨质量从而发挥抗骨质疏松的作用。