成骨生长肽羧基端片段衍生物H86A对去卵巢大鼠骨计量学的影响

目的 探讨成骨生长肽羧基端片段及其衍生物H86A对去卵巢(OVX)骨质疏松大鼠骨计量学的影响.方法 将32只3月龄SD雌性大鼠分为4组,1～3组行OVX手术,1、2组术后分别给予高低剂量的H86A,3组给予安慰剂,4组为假手术组(SHAM).12周后处死动物,分离左侧胫骨,制成不脱钙骨切片,检测并分析骨计量学有关指标.结果 H86A高剂量组(H86AH)与去卵巢给安慰剂组(OVX)比较,OV/BV减少(P＜0.01),其他指标无统计意义;与SHAM组比较,BV/TV、Tb.Th、Tb.N减少(P＜0.01),Tb.Sp、OV/BV增加(P＜0.01),其他指标无统计学意义(P＞0.05).H86A低剂量(H86AL)组与OVX组比较,BV/TV增加(P＜0.05),OV/BV减少(P＜0.01),sLS/BS、Ms/BS增加(P＜0.01),与SHAM组比较,BV/TV、Tb.Th、Tb.N减少(P＜0.01),Tb.Sp、OV/BV增加(P＜0.01),sLS/BS、MS/BS增加(P＜0.01),其他指标无统计学意义.结论 成骨生长肽羧基端片段及其衍生物可以提高骨量,改善骨组织的微结构,改善骨质疏松的骨质量.     

雌激素对去卵巢大鼠肝细胞胰岛素受体底物-1和2表达的影响

目的观察雌激素对去卵巢大鼠肝细胞胰岛素受体底物-1(IRS-1)和胰岛素受体底物-2(IRS-2)表达的影响,以探讨其改善胰岛素抵抗的机制。方法取6周SD雌性大鼠随机分为3组:假手术组(Sham组)、手术组(OVX组)和戊酸雌二醇组(E_2组),E_2组每天灌胃戊酸雌二醇水溶液(1 mg/kg),而其他组给予相应体积的蒸馏水,连续给药12周。然后采用葡萄糖氧化酶法测定血糖,实时荧光定量PCR法检测肝细胞IRS-1和IRS-2 mRNA的表达,免疫组织化学法检测肝细胞IRS-1和IRS-2蛋白的表达。结果 OVX大鼠终末体重、肝重、内脏脂肪指数KITT显著高于Sham组,而葡萄糖利用常数KITT显著低于Sham组(P0.05);与OVX组大鼠相比,E_2组大鼠终末体重、肝重、内脏脂肪指数显著降低,而葡萄糖利用常数显著升高(P0.05);免疫组化结果显示,OVX大鼠肝组织IRS-1、IRS-2表达阳性细胞数目及染色程度较Sham组显著减少,而雌激素替代治疗后肝组织IRS-2阳性表达细胞数目及染色程度显著改善,但IRS-1改善不显著;OVX大鼠肝细胞IRS-1和IRS-2mRNA表达水平显著低于Sham组,而E_2组大鼠IRS-1和IRS-2 mRNA表达水平显著高于OVX组(P0.05)。结论雌激素可上调去卵巢大鼠肝细胞IRS-1和IRS-2的表达水平,进而改善胰岛素抵抗。     

高原低压低氧环境对大鼠骨形态和微结构的影响研究

目的：研究长期暴露在高原低压低氧环境下大鼠骨形态和微结构的变化,探讨低压低氧环境对大鼠骨骼发育的影响。方法：将16只10周龄的SD大鼠按照体质量随机分为对照组和低压低氧组,每组8只。低压低氧组大鼠每天在低压低氧模拟氧舱中处理22 h,连续处理6周;对照组放置在正常大气压下,不作其他处理。实验过程中实时监测并记录大鼠的进食、体质量。使用游标卡尺测量右侧股骨长度;采用Micro-CT扫描测定大鼠右侧股骨远端干骺端皮质骨和骨小梁的微结构;计算骨组织的骨体积分数（BV/TV）、骨小梁数量（Tb.N）、骨小梁厚度（Tb.Th）和骨小梁的分离度（Tb.Sp）。使用SPSS 22.0软件进行统计学分析。结果：低压低氧处理2周到实验结束,低压低氧组大鼠的体质量始终小于对照组（P<0.05）;低压低氧处理1周到实验结束,低压低氧组大鼠的进食量始终少于对照组（P<0.05）;低压低氧组大鼠股骨长度及BV/TV、Tb.N、Tb.Th均显著小于对照组（P均<0.01）,Tb.Sp大于对照组（P<0.01）。MicroCT三维重建结果显示低压低氧组骨小梁的微结构受损,骨量明显降低,空间排...     

复方中药对慢性氟中毒大鼠氟骨症的骨形态计量学影响

目的 评价复方中药制剂对慢性氟中毒大鼠骨氟症的治疗效果。方法 取断乳2周的纯系Wistar大鼠88只,体重为（91.1±10.0） g,按体重应用随机数字表法分为对照组16只、中氟组(染氟剂量50 mg/kg)24只、高氟组（染氟剂量100 mg/kg)24只、高氟低钙低蛋白组（染氟剂量100 mg/kg,且蛋白质与钙的含量为中氟组和高氟组的一半)24只。染氟6个月后,各组采用股动脉放血法处死8只;染氟组余下的16只大鼠再分为2个小组,一组为持续染氟阳性对照组,另一组模拟氟病区实际情况,在持续染氟的基础上应用复方制剂进行治疗;分别在治疗前、治疗后30 d和60 d时收集大鼠24 h尿样。在灌服90 d时,处死大鼠,并分离四肢骨。尿氟含量用氟离子选择电极法测定。骨氟含量采用高温灰化-氟离子选择电极法法测定。用Micro-CT（显微CT）技术检测大鼠四肢骨骨矿物质密度（BMD）、组织骨密度（TMD）、结构模型指数（SMI）、骨小梁厚度（Tb.Th）、骨小梁分离度（Tb.Sp）、各向异性（a1/a3）、骨小梁连接密度（Conn.D）、骨小梁与全部骨组织体积比（BV/TV）、骨表面积与体积比（BS/BV）、骨小梁数目（Tb.N）。结果 应用复方中药治疗60 d时,中氟治疗组、高氟治疗组和高氟低钙低蛋白治疗组尿氟均低于相应的阳性对照组。用药90 d时,各治疗组骨氟亦低于相应的阳性对照组;中氟治疗组Conn.D［(1 443.81±684.09) mm-3］低于中氟阳性对照组［(2 403.68±124.02) mm-3］;高氟治疗组TMD［(500.16±85.63) mg/cc］、Conn.D［(856.22±329.92) mm-3］和BV/TV(0.44±0.04)低于相应的高氟阳性对照组［(639.96±9.51) mg/cc, (1 325.61±113.06) mm-3, (0.49±0.00)］。结论 综合尿氟、骨氟及四肢骨BMD、BV/TV等指标改变,提示该复方中药对大鼠氟骨症具有一定的治疗效果。     

橄榄油对大鼠去势后骨代谢指标及骨密度的影响

目的:观察橄榄油对去势后大鼠骨代谢和骨密度的影响,探讨并分析橄榄油防治绝经后骨质疏松症(PMOP)的有效性及机理。方法:将30只5～6个月龄清洁型SD雌性大鼠进行随机分成四组:①假手术组(Sham组)、②去卵巢组(OVX组)、③去卵巢+橄榄油组(OVX+Olive)、④去卵巢+雌激素组(OVX+E)。治疗组用药:(OVX+Olive)组及(OVX+E)组均采用经口灌胃方式进行用药,按1 ml/100 g体重,1次/天灌胃,连续12周。12周后分别左心室取血,检测血中雌二醇(E2)、血钙、血碱性磷酸酶(ALP)、白介素-6(IL-6)水平,放血处死后取出腰椎及左侧股骨行双能X线骨密度(DEXA)测定。结果:OVX组中血E2明显低于Sham组和治疗组,差异有统计学意义(P<0.01、P<0.05),ALP、IL-6值显著高于其余三组,差异有统计学意义(P<0.05);治疗组中E2、ALP、IL-6与Sham组差异无统计学意义(P>0.05);四组中血钙值差异均无统计学意义(P>0.05)。去势橄榄油组与雌激素组骨密度平均值均较OVX组高,差异有统计学意义(P<0.05),但该两组间差异无统计学意义(P>0.05)。结论:橄榄油能有效地减轻大鼠卵巢切除术引起的骨质丢失,可能通过补充植物雌激素发挥拟雌激素样作用。     

雌激素对去卵巢雌性大鼠子宫壁NPY-IRF的影响

目的:用SABC免疫组织化学染色法结合定量数据分析,探讨雌激素对去势雌性大鼠子宫壁神经肽Y免疫反应神经纤维(neuropeptide Y-immunoreactivity nerve fibers,NPY-IRF)的影响。方法:雌性SD大鼠分为假手术对照组(SHAM)、卵巢切除后4周组(OVX1)、卵巢切除后8周组(OVX2)、卵巢切除后肌注苯甲酸雌二醇4周组(OVX+E1)、卵巢切除后肌注苯甲酸雌二醇8周组(OVX+E2),共5组,每组10只,用SABC免疫组织化学染色法观察子宫壁NPY-IRF表达,实验数据进行统计学分析。结果:①OVX+E2组、SHAM组,NPY-IRF长,分支多;OVX+E1组NPY-IRF较长,分支较多;OVX1组及OVX2组,NPY-IRF较短,分支较少;②NPY-IRF表达概括为:OVX+E2组及SHAM组>OVX+E1组>OVX1组>OVX2组,P<0.05;OVX+E2组NPY-IRF表达与SHAM组相比差异无统计学意义,P>0.05。结论:子宫壁NPY-IRF的表达与雌激素水平呈正相关,雌激素水平高时,其表达增多;反之,则少。外源性雌激素对子宫壁NPY-IRF也有作用,但外源性雌激素是否能完全取代内源性雌激素还有待进一步研究。     

白藜芦醇对低压低氧诱导大鼠牙槽骨损伤的干预作用研究

目的 研究低气压缺氧环境对牙槽骨的损伤及白藜芦醇抗牙槽骨骨质疏松的效果。方法 雄性Wistar大鼠36只随机分为常氧组（control）、低压低氧组（hypoxia）和白黎芦醇干预组（Res），每组12只。采用低压氧舱模拟高原低压低氧环境，制备大鼠高原低氧模型，白藜芦醇干预组使用400mg/kg白藜芦醇进行灌胃，常氧组和低压低氧组使用0.5%羧甲基纤维素钠作为对照。各组处理9 w后进行动物安乐死并采集骨样本，通过Micro-CT、组织学染色及免疫组织化学染色分析，观察牙槽骨骨组织显微结构及成骨破骨分化情况。结果 Micro-CT及HE染色显示：与常氧组相比，低压低氧组大鼠下颌第一磨牙根分歧下方骨小梁变少且稀疏，牙根之间骨质破坏严重，BV/TV和Tb.N降低，Tb.Sp升高，差异均具有显著统计学意义（P<0.01）；与低压低氧组相比，白藜芦醇干预组大鼠骨小梁变化均趋于正常，BV/TV和Tb.N升高，Tb.Sp降低，差异具有统计学意义（P<0.05）。与常氧组相比，白藜芦醇干预组大鼠BV/TV和Tb.N降低，差异具有统计学意义（P<0.05）;Tb.Sp差异无统计学意义（...     

铝氟联合作用对大鼠骨生长和代谢影响的性别差异

目的通过骨形态计量学方法观察铝氟联合摄入对不同性别大鼠纵向骨生长及松质骨代谢的影响。方法 40只2月龄清洁级SD大鼠,雌雄各半,随机分成正常对照组(生理盐水)、铝+低氟组(0.1 mg/kg+5 mg/kg)、铝+中氟组(0.1 mg/kg+15 mg/kg)、铝+高氟组(0.1 mg/kg+30 mg/kg),每日灌胃1次,连续12周。实验结束时取胫骨近心端进行不脱钙骨切片和骨染色,观察生长板软骨以及干骺端骨小梁微结构改变,并进行骨代谢的定量分析。结果与对照组相比,铝+高氟组大鼠生长板总厚度增加(P0.01),且雄性大鼠出现凋亡软骨细胞。随氟染毒剂量的升高,初级小梁厚度(P.Tb.Wi)、骨小梁荧光周长(MS)、矿化沉积率(MAR)、骨形成率(BFR)等以及骨吸收周长(Er.S)均先升高(与对照组比较,P0.05或P0.01)后下降到接近对照组,铝+高氟组雄性的初级小梁厚度及骨形成参数甚至低于对照组(P0.05)。与对照组相比,铝+高氟组骨小梁体积(BV)、骨小梁数量(Tb.N)减少,小梁分离度(Tb.Sp)增加(P0.05),雌雄改变一致。结论铝和低剂量氟联合作用促进雌雄大鼠骨形成;铝和高剂量氟联合作用则抑制骨生长、抑制次级小梁骨形成和吸收,对雄性大鼠的效应更为明显。     

大豆异黄酮和补充钙对去卵巢大鼠骨密度及肝IGF-1mRNA表达的影响

目的 利用卵巢切除大鼠模型,研究大豆异黄酮和钙对卵巢切除大鼠骨密度及肝脏IGF-1基因表达的影响.方法 将6月龄雌性SD大鼠,按体重随机分成5组假手术组(Sham)、卵巢切除阴性对照组(OVX)、单纯大豆异黄酮组(SI)、单纯碳酸钙组(Ca)、大豆异黄酮加碳酸钙组(SI+Ca).所有大鼠饲以钙含量为3.732g/kg的低钙饮食喂养12周.实验结束时,利用双能X线骨密度扫描仪测量右侧股骨骨密度(BMD),采用逆转录-聚合酶链反应(RT-PCR)方法测定肝脏胰岛素样生长因子-1(IGF-1)基因表达水平.结果 SI+Ca组股骨远心端BMD为(0.263±0.007)g/cm2,Sham组为(0.267±0.008)g/cm2,两组间差异无统计学意义,但这两组BMD均显著性高于OVX(0.245±0.005)g/cm2、SI(0.258±0.011)g/cm2和Ca(0.255±0.004)g/cm2组(P＜0.05).肝脏IGF-1mRNA表达水平在Sham(0.200±0.023)g/cm2、SI(0.278±0.019)g/cm2、Ca(0.302±0.026)g/cm2及SI+Ca(0.231±0.025)g/cm2组中均显著性低于OVX(0.362±0.031)g/cm2,P＜0.05,SI+Ca组IGF-1mRNA表达水平(0.231±0.025)g/cm2低于SI(0.278±0.019)g/cm2和Ca(0.302±0.026)g/cm2两组,并差异有统计学意义.结论 SI+Ca能比单纯喂饲SI或Ca更好地防止卵巢切除大鼠股骨BMD的减小.37.95 mg/kg剂量的SI能够显著抑制由于卵巢切除引起的肝脏IGF-1 mRNA表达水平的上升.     

运动对去卵巢大鼠骨矿含量和骨密度的影响

目的观察运动对去卵巢大鼠骨矿含量(bone mineral contant,简称BMC)和骨密度(bonemineral density,简称BMD)的影响。方法雌性(sprague daivley,简称SD)大鼠随机分为正常对照组(SHAM)、去卵巢手术对照组(OVX)、雌激素治疗组(OVX+ES)、运动组(OVX+ET)。SHAM组行假手术,其余各组行双侧卵巢切除术,术后75天开始为期3个月的治疗。OVX+ES组用尼尔雌醇治疗,OVX+ET组按要求进行运动。治疗结束后检测股骨和胫骨的BMC和BMD。结果股骨BMD比较,SHAM组(0.206±0.009)高于OVX组(0.196±0.012),差异有统计学意义(P<0.05);胫骨BMC比较,OVX+ET组(0.298±0.033)高于OVX组(0.260±0.033),差异有统计学意义(P<0.05);胫骨BMD比较,OVX组比其它3组均低,差异有统计学意义(P<0.05或P<0.01);运动明显提高去卵巢大鼠胫骨的BMC和BMD,运动在提高胫骨BMD方面的功效优于激素疗法。结论运动对绝经后骨质疏松症的形成有一定干预作用。     

Kefir Peptides Prevent Estrogen Deficiency-Induced Bone Loss and Modulate the Structure of the Gut Microbiota in Ovariectomized Mice

Osteoporosis is a major skeletal disease associated with estrogen deficiency in postmenopausal women. Kefir-fermented peptides (KPs) are bioactive peptides with health-promoting benefits that are produced from the degradation of dairy milk proteins by the probiotic microflora in kefir grains. This study aimed to evaluate the effects of KPs on osteoporosis prevention and the modulation of the composition of the gut microbiota in ovariectomized (OVX) mice. OVX mice receiving an 8-week oral gavage of 100 mg of KPs and 100 mg of KPs + 10 mg Ca exhibited lower trabecular separation (Tb. Sp), and higher bone mineral density (BMD), trabecular number (Tb. N) and bone volume (BV/TV), than OVX groups receiving Ca alone and untreated mice, and these effects were also reflected in bones with better mechanical properties of strength and fracture toughness. The gut microbiota of the cecal contents was examined by 16S rDNA amplicon sequencing. α-Diversity analysis indicated that the gut microbiota of OVX mice was enriched more than that of sham mice, but the diversity was not changed significantly. Treatment with KPs caused increased microbiota richness and diversity in OVX mice compared with those in sham mice. The microbiota composition changed markedly in OVX mice compared with that in sham mice. Following the oral administration of KPs for 8 weeks, the abundances of Alloprevotella, Anaerostipes, Parasutterella, Romboutsia, Ruminococcus_1 and Streptococcus genera were restored to levels close to those in the sham group. However, the correlation of these bacterial populations with bone metabolism needs further investigation. Taken together, KPs prevent menopausal osteoporosis and mildly modulate the structure of the gut microbiota in OVX mice.     

大豆异黄酮类对去卵巢大鼠骨丢失的影响

目的　研究大豆中植物雌激素——异黄酮类对去卵巢大鼠骨丢失的预防作用。方法　将 3月龄 SD雌性大鼠按体重分为 5组 ,每组 1 1只 :假手术对照组 (假手术 +饲含酪蛋白饲料 ,Sham) ;去异黄酮组 (去卵巢 +饲含去异黄酮类大豆分离蛋白饲料 ,Soy- ) ;异黄酮组 (去卵巢 +饲含异黄酮类大豆分离蛋白饲料 ,Soy+) ;酪蛋白组 (去卵巢 +饲含酪蛋白饲料 ,即去卵巢对照组 ,Ovx) ;雌激素对照组 (去卵巢 +饲含酪蛋白饲料 +注射雌二醇 ,E2 )。在实验期第 3周、第 6期和第 9周各进行为期三天的钙代谢试验。第 1 0周末处死大鼠 ,测定骨钙、骨密度 ,并对股骨远端松质骨进行骨组织形态学测量。结果　异黄酮组和雌激素对照组粪钙、尿钙排出量显著低于酪蛋白组和去异黄酮组 (P<0 .0 5) ,钙表观吸收率和钙贮留量显著高于酪蛋白组和去黄酮组 (P<0 .0 5) ,钙代谢呈正平衡。异黄酮组和雌激素对照组骨钙、骨密度高于酪蛋白组和去异黄酮组 (P<0 .0 5)。与雌激素对照组比较 ,异黄酮组骨小梁面积百分率和骨小梁数目明显减少 ,骨小梁间隙明显增宽 (P<0 .0 5) ;但与酪蛋白组和去异黄酮组比较 ,异黄酮组骨小梁面积百分率和骨小梁数目明显增多 ,骨小梁间隙明显减少 (P<0 .0 5)。结论　含有异黄酮类的大豆分离蛋白具有预防骨丢失的作用 ,而?     

Pharmacological and Non-Pharmacological Agents versus Bovine Colostrum Supplementation for the Management of Bone Health Using an Osteoporosis-Induced Rat Model

Osteoporosis is defined by loss of bone mass and deteriorated bone microarchitecture. The present study compared the effects of available pharmacological and non-pharmacological agents for osteoporosis [alendronate (ALE) and concomitant supplementation of vitamin D (VD) and calcium (Ca)] with the effects of bovine colostrum (BC) supplementation in ovariectomized (OVX) and orchidectomized (ORX) rats. Seven-month-old rats were randomly allocated to: (1) placebo-control, (2) ALE group (7.5 μg/kg of body weight/day/5 times per week), (3) VD/Ca group (VD: 35 μg/kg of body weight/day/5 times per week; Ca: 13 mg/kg of body weight/day/3 times per week), and (4) BC supplementation (OVX: 1.5 g/day/5 times per week; ORX: 2 g/day/5 times per week). Following four months of supplementation, bone microarchitecture, strength and bone markers were evaluated. ALE group demonstrated significantly higher Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC and significantly lower Ct.Pr, Tb.Pr, Tb.Sp, Ct.BMD and Tb.BMD, compared to placebo (p < 0.05). BC presented significantly higher Ct.Pr, Ct.BMD, Tb.Pr, Tb.Sp, and Tb.BMD and significantly lower Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC compared to ALE in OVX rats (p < 0.05). OVX rats receiving BC experienced a significant increase in serum ALP and OC levels post-supplementation (p < 0.05). BC supplementation may induce positive effects on bone metabolism by stimulating bone formation, but appear not to be as effective as ALE.     

雌激素和维生素K抗去势成年雌性大鼠骨质疏松的实验研究

目的寻找一种或一组简便有效,价格低廉的防治骨质疏松（osteoporosis,OP）的方法,以期为防治骨质疏松药物的开发提供实验依据。方法以去卵巢雌性SD大鼠作为绝经早期骨质疏松模型。将50只SD雌性大鼠随机分为5组：卵巢去势（ovariectomized,OVX）组（OVX组,n=10）、卵巢去势＋雌激素组（OVX＋E组,n=10）、卵巢去势＋维生素K组（OVX＋vit K组,n=10）和卵巢去势＋雌激素＋维生素K组（OVX＋E＋vitK组,n=10）、假手术组（sham组,n=10）。卵巢去势1个月后,分组给药,8周后集中统一处死,取左侧股骨检测骨密度（bone mineral density,BMD）,右侧股骨病理学切片进行骨小梁形态计量观察,取右心室血清检测白介素（interleukin,IL）-6、骨钙素（bone gla protein,BGP）和胰岛索样生长因子（insulin-like growth factor,IGF）-1含量。结果①OVX组与sham组比较,骨密度显著下降,血清白介素-6和骨钙素测量值明显升高,而胰岛素生长因子-1显著下降,表明造模成功。②OVX组骨组织病理学切片40倍光镜下骨小梁形态计量观察结果与sham组、OVX＋vitK组、OVX＋E组和OVX＋E＋vit K组比较,差异有显著意义。其中,OVX＋E＋vit K组与sham组最相似。③OVX＋E组与OVX组比较,股骨干骺端（松质骨）骨密度显著升高,而股骨中段（皮质骨为主）骨密度升高,差异无显著意义。OVX＋vitK组与OVX组比较,股骨中段（皮质骨）骨密度显著升高,股骨干骺端（松质骨为主）骨密度升高,但差异无显著意义。OVX＋E＋vitK组股骨干骺端和股骨中段骨密度均显著性升高,与sham组最接近。④OVX＋E组与OVX组比较,血清白介素-6含量和骨密度低,胰岛素生长因子-1含量升高,差异有显著意义;OVX＋vitK组与OVX组比较,血清白介素-6测量值低,骨钙素和胰岛素生长因子-1测量值升高,差异有显著意义;OVX＋E＋vitK组血清白介素-6,骨钙素和胰岛素生长因子-1含量与sham组比较,最为接近。结论①去卵巢大鼠骨密度及骨形成指标胰岛素生长因子-1下降,骨吸收指标白介素-6、骨吸收和骨形成指标骨钙素升高,表明绝经早期骨代谢处于骨吸收大于骨形成的高转换状态,导致骨质疏松。②雌二醇（estrogen,E2）水平下降是骨质疏松的一个重要致病因素。病理形态学观察和骨密度及血清白介素-6、骨钙素、胰岛素生长因子-1含量检测表明,维生素K和雌激素防治骨质疏松均有效,二者联合用药的作用明显优于单一用药。     

复方丹参合剂对去卵巢大鼠骨元素代谢的影响

目的:观察复方丹参合剂对抗去卵巢大鼠骨元素代谢紊乱的作用。方法:将健康4月龄雌性SD大鼠36只,随机分成6组。A组(正常对照);B组(假去卵巢);C组(去卵巢);D组(去卵巢+合剂小剂量);E组(去卵巢+合剂中等剂量);F组(去卵巢+合剂大剂量)。去卵巢后第2 d开始,连续用药11周。用测定骨元素含量的方法,分析了复方丹参合剂(三种不同浓度)对切除双侧卵巢后的大鼠骨矿物元素代谢的影响。结果:去卵巢大鼠骨Ca、S、Mg、Mn等元素明显降低,骨P含量增加,复方丹参合剂可使去卵巢大鼠降低的骨Ca、S、Mg、Mn等矿物元素均显著回升,骨P回降。结论:复方丹参合剂具有良好的对抗由于去卵巢引起骨元素代谢紊乱作用。     

Equol, a metabolite of daidzein, inhibits bone loss in ovariectomized mice

Soybean isoflavones have structures similar to that of estrogen and have received attention as alternatives to hormone replacement therapy for the prevention of postmenopausal osteoporosis. Daidzein, a major isoflavone found in soybean, is metabolized to equol by gut microflora, and the metabolite exhibits a stronger estrogenic activity than daidzein. However, there is no direct evidence that equol affects bone metabolism. In this study, we examined the effect of equol on the inhibition of bone loss in ovariectomized (OVX) mice. Female mice (8 wk old) were assigned to 5 groups as follows: sham-operated (sham), OVX, OVX + 0.1 mg/d equol administration (0.1 Eq), OVX + 0.5 mg/d equol administration (0.5 Eq), and OVX + 0.03 microg/d 17beta-estradiol administration (E(2)). Equol and E(2) were administered s.c., using a mini-osmotic pump. At 4 wk after the intervention, uterine weight was less in the OVX mice than in sham-operated mice (P < 0.05). The weight was maintained in the E(2) group. In contrast, administration of equol at doses used in this study did not affect uterine atrophy in OVX mice. Bone mineral density (BMD) for the whole body in the OVX group measured by dual-energy X-ray absorptiometry was lower than that in the sham group, whereas administration of 0.5 mg/d Eq as well as E(2) maintained the BMD. The BMD of the femur and lumbar spine in the OVX group was also lower than those in the sham group, and treatment with 0.5 mg/d Eq maintained it. Notably, the BMD of the proximal femur in the 0.5 Eq group was the same as that of the sham group. E(2) inhibited bone loss from all regions induced by OVX. These results suggest that equol, a major metabolite of daidzein, inhibits bone loss apparently without estrogenic activity in the reproductive organs of OVX mice.     

Menaquinone 4 Reduces Bone Loss in Ovariectomized Mice through Dual Regulation of Bone Remodeling

Epidemiologic studies showed that higher vitamin K (VK) consumption correlates with a reduced risk of osteoporosis, yet the dispute remains about whether VK is effective in improving bone mineral density (BMD). We sought to discover the anti-osteoporotic effect of menaquinone-4 (MK-4) and evaluate the expression of critical genes related to bone formation and bone resorption pathways in the body. Fifty female C57BL/6 mice (aged 13 weeks) were randomly arranged to a sham-operated group (SHAM, treated with corn oil) and four ovariectomized groups that were administered corn oil (OVX group), estradiol valerate (EV, 2 mg/kg body weight as the positive control), low or high doses of VK (LVK and HVK; 20 and 40 mg MK-4/kg body weight, respectively) by gavage every other day for 12 weeks. Body and uterine weight, serum biochemical indicators, bone microarchitecture, hematoxylin-eosin (HE) staining, and the mRNA expression of critical genes related to bone formation and bone resorption pathways were assessed. Either dose of MK-4 supplementation increased the alkaline phosphatase (ALP), decreased the undercarboxylated osteocalcin (ucOC) and tartrate-resistant acid phosphatase (TRACP, p < 0.05) levels, and presented higher BMD, percent bone volume (BV/TV), trabecular thickness (Tb.Th), and lower trabecular separation (Tb.Sp) and structure model index (SMI, p < 0.05) compared with the OVX group. Additionally, both doses of MK4 increased the mRNA expression of Runx2 and Bmp2 (p < 0.05), whereas the doses down-regulated Pu.1 and Nfatc1 (p < 0.05) mRNA expression, the high dose decreased Osx and Tgfb (p < 0.05) mRNA expression, and the low dose decreased Mitd and Akt1 (p < 0.05) mRNA expression. These data show the dual regulatory effects of MK-4 on bone remodeling in ovariectomized mice: the promotion of bone anabolic activity and inhibition of osteoclast differentiation, which provides a novel idea for treating osteoporosis.     

硫酸软骨素加钙对卵巢切除大鼠骨密度和骨钙含量的影响

目的探讨硫酸软骨素加钙对卵巢切除大鼠模型骨密度和骨钙含量的影响。方法选用卵巢切除大鼠所诱发的骨质疏松模型，给予硫酸软骨素加钙治疗，同时设假手术组及模型对照组。3个月后测定大鼠骨密度、骨钙含量。结果发现假手术组和高剂量组大鼠股骨骨密度和股骨钙含量显著高于阴性对照组（P〈0．05）。结论表明硫酸软骨素加钙能增加卵巢切除大鼠的骨密度，对雌激素缺乏所诱发的骨钙丢失具有抑制作用。     

The Brown Algae Ishige sinicola Extract Ameliorates Ovariectomy-Induced Bone Loss in Rats and Suppresses Osteoclastogenesis through Downregulation of NFATc1/c-Fos

Osteoporosis is characterized by reduction in bone mass and microarchitectural deterioration of the bone, which causes bone fragility and fracture susceptibility. Ishige sinicola, a brown alga, reportedly affects osteoblast differentiation. However, its protective effect on estrogen deficiency-induced bone loss has not been elucidated. This study aimed to investigate the effect of I. sinicola extract (ISE) on ovariectomy (OVX)-induced bone loss in vivo and osteoclastogenesis in vitro. Female Sprague-Dawley rats were randomly assigned to the sham-operated (SHAM) group and four OVX subgroups: SHAM, OVX, ISE20 (20 mg/kg), ISE200 (200 mg/kg), and estradiol (10 μg/kg). After 6 weeks of treatment, the bone mineral density (BMD), femur indices, and serum biomarker levels were measured. Furthermore, the effects of ISE on osteoclastogenesis and the expression of osteoclast-specific markers were measured. ISE administration improved the trabecular bone structure, bone biomechanical properties, BMD, and bone mineralization degree. In addition, the levels of serum bone turnover markers were decreased in the ISE group compared with those in the OVX group. Moreover, ISE inhibited osteoclast formation by downregulating NFATc1, TRAP, c-Src, c-Fos, and cathepsin K without any cytotoxic effects on RANKL-induced osteoclast formation. Therefore, we suggest that ISE has therapeutic potential in postmenopausal osteoporosis.