补肾益精方对去卵巢骨质疏松大鼠皮质骨生物力学性能的改善作用及机制探讨

目的：探讨补肾益精方对去卵巢骨质疏松模型大鼠皮质骨（股骨）生物力学性能的作用及相关机制。方法：将40只10月龄Wistar雄性大鼠随机分为正常对照组、模型对照组、补肾益精方组和倍美力组,每组10只。正常对照组做假手术,其余4组做卵巢切除术。术后正常饲养90天,第91天开始给药,连续用药90天,处死,测定股骨的骨矿密度和几何尺寸及股骨的生物力学性能。结果：模型大鼠股骨的生物力学性能明显下降,骨强度降低,股骨干外径变细,股骨中段骨皮质面积减少,股矿密度有所减少。补肾益精方组大鼠股骨的生物力学性能明显提高,骨强度增加;股骨中段外径增粗,骨皮质面积增加,骨矿密度有所增加。结论：补肾益精方能明显改善去卵巢骨质疏松模型大鼠皮质骨（股骨）的生物力学性能。其主要作用机制是：补肾益精方能够提高大鼠皮质骨（股骨）宏观结构的生物力学应答调节机能,使股骨干外径增粗,皮质骨面积增加,骨矿密度有所提高。     

南极磷虾肽对去卵巢大鼠骨质疏松症的改善作用

目的：观察南极磷虾肽(peptides from Antarctic krill, AKP)对去卵巢大鼠骨代谢、骨密度(BMD)及骨生物力学的影响,探讨其对骨质疏松症的改善作用。方法：32只雌性Wistar大鼠随机分为4组：假手术组、模型对照组、阳性对照组(阿伦磷酸钠1mg/(kg.d))和南极磷虾肽组(1000mg/(kg.d)),大鼠摘除双侧卵巢后4周开始持续灌胃90d,分别检测血清雌二醇(E2)、血清骨代谢指标(骨源性碱性磷酸酶(BALP)、骨钙素(OCN)、I型前胶原羧基端前肽(PICP)、组织蛋白酶K(Cath-K)、I型胶原羧基端交联肽(CTX-I))和尿液中骨代谢指标(钙(Ca)、磷(P)、脱氧吡啶啉(DPD))含量,并测定大鼠骨密度和骨生物力学指标。结果：南极磷虾肽能显著改善去卵巢大鼠血清中BALP、OCN和PICP的分泌(P<0.01),降低血清Cath-K、CTX-I和尿Ca、P、DPD水平(P<0.01),改善去卵巢大鼠骨代谢的高转换率;南极磷虾肽能显著增加去卵巢大鼠BMD(P <0.01),改善其骨生物力学性能(P <0.01)。结论：南极磷虾肽具有改善去卵巢大鼠骨质疏松症的作用。     

骨新康对去卵巢大鼠骨质疏松症的治疗作用

目的观察骨新康对卵巢切除致大鼠骨质疏松症的治疗作用。方法选用SD雌性大鼠,随机分为7组,每组12只,一组切去腹腔中少量脂肪作为假手术组,其余各组大鼠切除双侧卵巢,3个月后各组干预给药,8周后测定各组股骨骨密度、骨生物力学指标、骨显微结构,以及大鼠血清生化指标。结果骨新康具有增加骨密度、改善骨生物力学指标以及具有性激素和促性腺激素样作用。结论该药物具有抗大鼠骨质疏松症的作用。     

复方碳酸钙泡腾颗粒对大鼠骨质疏松的药效学研究

目的:探讨复方碳酸钙泡腾颗粒对大鼠骨质疏松的防治作用.方法:建立维A酸造成大鼠骨质疏松动物模型,观察大鼠模型的钙磷含量和股骨骨密度;建立缺乏维生素D(避光饲养)致佝偻病大鼠模型,观察大鼠模型的钙磷含量和股骨骨密度.结果:复方碳酸钙泡腾颗粒可使造模成功大鼠的骨密度增加,骨皮质增厚,骨畸形明显改善.结论:复方碳酸钙泡腾颗粒可增加骨钙含量和骨密度,对骨质疏松和佝偻病有较好的防治作用.     

补肾益肝活血胶囊对去卵巢大鼠骨生物力学的影响

目的观察补肾益肝活血胶囊对大鼠去卵巢骨生物力学的影响。方法6月龄大鼠随机分为假手术组(N)、模型组(O)、模型 尼尔雌醇处理组(O E)、模型 补肾益肝活血胶囊处理组(O M)。治疗12周后，在乙醚麻醉下处死大鼠，行大鼠股骨骨载荷、骨桡度、骨强度、韧性等生物力学指标测定。结果模型 补肾益肝活血胶囊处理组(O M)所有生物力学指标明显好于模型组(O)，差异有显著意义。结论补肾益肝活血胶囊可明显改善去卵巢大鼠骨生物力学状态，提高骨骼抵抗外力冲击的能力，有效的防治大鼠去卵巢后引起的骨质疏松症，避免骨折的发生。     

柚皮素防治去卵巢致大鼠骨质疏松症的实验研究

研究柚皮素对去卵巢致大鼠骨质疏松骨代谢及相关组织生化指标的影响。选取32只3月龄未经产雌性Sprague-Dawley(SD)大鼠,随机分为4组:假手术组(Sham)、去卵巢模型组(OVX)、17β-雌二醇治疗组(E2)和柚皮素治疗组(Naringenin),每组灌胃相应药物,给药12周后收集大鼠24 h尿液,麻醉动物采集血清,处死后解剖大鼠取以下标本进行分析:称重考察各脏器系数;制作石蜡切片观察子宫病理变化;采用全自动生化分析仪对血清肝肾功能指标进行分析;ELISA等免疫学方法对骨转换指标血清骨钙素(BGP)和尿液脱氧吡啶啉(DPD)进行测定;采用三点弯曲实验对股骨生物力学性能进行分析;采用DEXA骨密度测定仪及Micro CT对骨矿密度(BMD)、骨矿含量(BMC)及干骺端骨小梁微组织结构进行测定。结果发现柚皮素可以对抗卵巢切除引起的大鼠体重增加,抑制骨转换指标BGP和DPD含量的升高,降低骨转换率,保持骨矿密度,改善骨应力和弹性模量等内在特性指标,同时骨小梁微结构也有了显著改善;另外,对肝肾功能未产生明显影响。可见柚皮素对去卵巢致大鼠骨质疏松有明显的防治作用,具有开发为妇女绝经后骨质疏松症治疗药物的潜在价值。     

仙葛颗粒对去卵巢骨质疏松大鼠模型的影响

目的观察仙葛颗粒对去卵巢骨质疏松大鼠模型的影响,探究其防治骨质疏松症的机制。方法将60只雌性大鼠随机分成空白对照组,模型组,仙葛颗粒低、中、高剂量组,尼尔雌醇组共6组。采用卵巢切除的方法制成绝经后骨质疏松动物模型,灌胃给药3个月后测定股骨骨密度及降钙素、骨钙素、雌二醇含量,取股骨下段松质骨进行电镜观察。结果仙葛颗粒能明显提高去卵巢大鼠模型血清降钙素、骨钙素和雌二醇水平,显著增加其骨密度值,改善松质骨的微结构。结论仙葛颗粒对骨质疏松症有防治作用。     

染料木素对去卵巢大鼠骨代谢的影响

目的　探讨染料木素对去卵巢所致骨质疏松模型大鼠的影响。方法　SD大鼠 36 0只 ,随机分为 7组 :正常对照组、模型组、骨疏康组、尼尔雌醇组和染料木素大、中、小剂量组。各组大鼠切除双侧卵巢 (正常对照组行假手术 ) ,术后第 8天开始ig给药 ,并分别于不同时间点从各组取 10只大鼠对体质量、血生化、BMD和生物力学等指标进行测定。结果　染料木素可抑制去卵巢模型大鼠的体质量增加 ,使模型大鼠的血清Ca、Mg、P、CT水平明显升高 ,BGP、ALP水平降低 ,与正常对照组有显著差异 ;在 4 .5、9mg·kg-1时可显著增强模型大鼠的股骨、胫骨和腰椎L2 - 4的BMD ;对模型大鼠的股骨生物力学指标有明显改善(P <0 .0 5或P <0 .0 1)。结论　染料木素可明显改善去卵巢模型大鼠的血生化指标、骨密度和生物力学指标 ,对骨质疏松有较好的疗效。     

黄柏小檗碱对去卵巢大鼠骨质疏松症的作用

目的：研究黄柏小檗碱对去卵巢大鼠骨质疏松症的作用.方法：去卵巢以建立大鼠骨质疏松症模型,将大鼠随机分为假手术组、去卵巢组,尼尔雌醇组及低（10 mg/kg）、中（30 mg/kg）、高（90 mg/kg）剂量黄柏小檗碱组进行实验,每组10只.12周后,以比色法测定其血清钙、磷的浓度和碱性磷酸酶的活性,竞争放射免疫法测定血清中骨钙素、降钙素、甲状旁腺素及雌二醇的浓度;双能X射线骨密度仪测定大鼠股骨干骺端的骨密度.结果：黄柏小檗碱能够增加去卵巢大鼠子宫重量、股骨干骺端的骨密度和血清无机磷含量;降低碱性磷酸酶活性和甲状旁腺素浓度,增加血清雌二醇、骨钙素、降钙素浓度.结论：黄柏小檗碱对去卵巢大鼠骨质疏松症具有防治作用,其机制可能是抑制骨吸收、促进骨形成,促进雌二醇和降钙素合成.     

口服水溶性钙补充剂促进大鼠生长发育研究

目的 研究口服水溶性钙补充剂对大鼠生长发育情况的影响。方法 将断乳的四周龄雌性SD大鼠随机分为5组，包括低、中、高剂量水溶性钙组，高剂量碳酸钙对照组和基础饲料对照组，每组10只，经口灌胃给予受试物，实验周期7周，并对大鼠体重、身长、股骨长、股骨干重、股骨骨密度、股骨骨钙含量等关键性生长发育指标进行统计分析。结果 低、中、高剂量水溶性钙组大鼠股骨的骨干重、骨钙含量和骨密度均显著大于基础饲料组（P<0.05），高剂量水溶性钙组的股骨骨长显著高于基础饲料组（P<0.05），高剂量水溶性钙组与高剂量碳酸钙对照组大鼠股骨的骨钙含量及骨密度均无显著差异（P>0.05），股骨长和股骨干重显著大于碳酸钙对照组（P<0.05），高剂量水溶性钙组大鼠的体重及身长均显著高于碳酸钙对照组（P<0.05）。结论 口服水溶性钙补充剂具有良好的补钙效果，是作为钙补充剂的较佳选择。     

Effect of angiotensin II type 1 receptor blocker on osteoporotic rat femurs

BackgroundOsteoblasts and osteoclasts are known to express Ang II type I (AT1) receptor in cell cultures, suggesting the existence of local renin-angiotensin system (RAS) in bone. This study was designed to investigate the effects of losartan as AT1 receptor blocker on ovariectomized rats' femur.MethodsLosartan (5 mg/kg/day) was administered via oral gavage for 8 weeks. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, while tensile and three-point bending tests were performed for evaluation of biomechanical properties of bone. The trabecular porosity was analyzed by scanning electron microscopy.ResultsThere was a significant decrease in BMD values of ovariectomized rats' femurs which were reversed by losartan treatment. According to tensile test results, ultimate tensile strength and strain values of losartan treated ovariectomized rats' femurs increased and decreased, respectively, when compared to that of ovariectomized animals. Losartan treatment also caused a significant recovery in flexural strength and modulus parameters regarding respective control values, which mean losartan treated ovariectomized rats' femur had more force tolerance until break than ovariectomized rats' femur. Quantitative microscopic analysis showed larger trabecular porosity in ovariectomized rats than control rat femurs and it was significantly decreased after losartan treatment.ConclusionBlockage of AT1 receptor increased strength, mass and trabecular connections of ovariectomized rat femurs. Therefore, it is tempting to speculate that drugs, including AT1 receptor blockers, may be used for the treatment of osteoporosis or reduction of its detrimental effects in the future.     

基于尿液代谢组学研究豆豉抗骨质疏松作用机制

目的探究豆豉对去卵巢骨质疏松大鼠骨代谢的影响及作用机制。方法将3月龄SPF级SD♀大鼠随机分为假手术组、模型组、雌二醇组及豆豉组,每组8只。手术后1周,通过灌胃将相应药物给予8周。8周后,测量每组的骨矿物质密度(BMD)和子宫指数,利用尿液代谢组学方法鉴定切除卵巢骨质疏松大鼠的生物标记物。结果(1)豆豉可明显增加模型组去卵巢大鼠股骨的BMD、子宫指数,明显降低模型组去卵巢大鼠体质量。(2)确定了与绝经后骨质疏松症密切相关的23个生物标记物及9条代谢通路。豆豉通过调节多种代谢途径,例如肌醇磷酸代谢、初级胆汁酸生物合成代谢和嘌呤代谢,可明显对12个生物标记物产生回调作用。结论豆豉能够有效干预绝经后骨质疏松症的发生和发展,该研究为预防绝经后骨质疏松症药物的研究与开发提供科学的依据。     

补骨脂素对绝经后大鼠骨质疏松及PI3K/Akt/mTOR信号通路的影响

目的:研究补骨脂素对绝经后大鼠骨质疏松及磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的影响。方法:将60只健康雌性SD大鼠随机分为正常组、模型组、阳性对照组(0.09 mg/kg雌二醇)和补骨脂素低、中、高剂量组(22、44、88 mg/kg),每组10只。除正常组外,其余各组大鼠均采用卵巢摘除去势法建立绝经后骨质疏松模型。术后正常饲养2个月,正常组和模型组大鼠灌胃等体积生理盐水,各药物组大鼠灌胃相应药液;灌胃体积均为0.005 mL/g,每天1次,连续98天。末次给药24 h后,测定大鼠右侧下肢股骨和椎骨的骨密度,血清中钙离子、骨钙素、Ⅰ型前胶原N端前肽(P1NP)含量和骨形态发生蛋白2(BMP2)、血管内皮生长因子(VEGF)水平,以及股骨组织中PI3K、Akt、mTOR mRNA及蛋白的表达水平。结果:与正常组比较,模型组大鼠股骨和椎骨的骨密度以及血清中钙离子、骨钙素、P1NP含量和BMP2、VEGF水平均显著降低,PI3K、Akt、mTOR mRNA及蛋白的表达水平均显著升高(P<0.05或P<0.01)。与模型组比较,补骨脂素中、高剂量组和阳性对照组大鼠股骨和椎骨的骨密度以及血清中钙离子、骨钙素、P1NP含量和BMP2(补骨脂素中剂量组除外)、VEGF(补骨脂素中剂量组除外)水平均显著升高,各药物组PI3K、Akt、m TOR mRNA(补骨脂素低剂量组除外)及蛋白表达水平均显著降低(P<0.05或P<0.01),且高剂量组股骨骨密度和钙离子、BMP2水平以及PI3K蛋白表达水平均显著高于阳性对照组(P<0.05),mTOR mRNA表达水平显著低于阳性对照组(P<0.05)。结论:补骨脂素可改善绝经后大鼠的骨质疏松,其机制可能与抑制PI3K/Akt/mTOR信号通路有关。     

Effect of Bixieqianggupian on experimental osteoporosis in rats

Objective To search the effects of Bixieqianggupian(BXQBP)on osteoporosis.Methods The experimental models of osteoporosis(OP)induced by ovariectomy(OVX),retinoic acid(RA)and dexamethasone(DXM)in rats were introduced in this study.In the same time,the influence on tibia fracture healing in rats was also observed.Moreover,the anti-inflammation effects and analgesia of BXQBP in mice and rats were also studied.Results The body weight gain induced by OVX was prevented obviously by administering BXQBP.And serum estradiol and bone gla protein(BGP)were examined by RIA,and results showed that estradiol increased and BGP decreased.Bone mineral density(BMD),bone mineral content(BMC)and bone mass of femur had increased,moreover,calcium content of bone(monitored by atomic absorption)had been improved significantly after BXQBP administration.Furthermore,biomechanical characters of bone were measured by three point bending test,and the anti-bend intensity and maximum bend strength increased remarkably.The alkaline phosphatese(ALP)decreased.And amount of urine calcium(Ca)and hydroxyproline(HOP)decreased obviously.However,effect on the proliferation of endometria was not obvious.The RA induced OP model.Compared with model,the BMD and BMC increased markedly in BXQBP rats(i.g.30 days).And bone mass and calcium content were increased.Then BGP and ALP decreased by administering BXQBP.The anti-band intensity and maximum bend strength increased evidently.And ejection of urine Ca and HOP decreased obviously.The bone trabecula became thinner,and arranged in disorder in OP rats,however,the status was reversed obviously by administrating BXQBP.The OP model also induced by DXM in rats:Effect against weight losing caused by DXM was observed in groups of three doses(i.g.12 weeks)of BXQBP.And BMD,BMC,bone mass and calcium content increased evidently.The results showed that the fracture healing had been enhanced obviously at three doses(i.g.40 days),callus growth was promoted and bone rigidity was reinforced.Moreover,BXQBP had the anti-inflammation and analgesia effects in mice and rats.Conclusions These results indicated that BXQBP had an obviously protective effect on osteoporosis in experimental animals,and promoted the fracture healing.     

骨立拮抗维甲酸所致大鼠骨质疏松的实验研究

目的　观察骨立对维甲酸所致骨质疏松大鼠的股骨骨密度、骨矿含量的影响。方法　采用ig维甲酸造成大鼠骨质疏松模型 ,使用骨立高、中、低 3种剂量分别进行治疗 ,观察其结果并与空白对照组和阳性对照药物组进行比较。结果　骨立 3个剂量治疗的骨质疏松大鼠的股骨骨密度和骨钙、骨磷含量均明显高于骨质疏松模型组大鼠 (P <0 .0 1或 0 .0 5 ) ,骨立高、中剂量组大鼠的尿钙排泄量明显低于骨质疏松模型组大鼠 (P <0 .0 1) ,其中以高剂量组疗效最佳。结论　骨立可明显提高骨质疏松大鼠的骨密度并升高其骨钙、骨磷的含量 ,降低尿钙排泄量 ,从而拮抗维甲酸所致的大鼠骨质疏松症。     

骨元肽结肠溶胶囊对去卵巢大鼠骨质疏松症的防治作用

目的探讨骨元肽结肠溶胶囊对去卵巢大鼠引起骨质疏松症的防治作用。方法采用切除大鼠双侧卵巢的方法建立大鼠骨质疏松症模型,以雌二醇(E2)作阳性对照,用放射免疫法检测大鼠血清中E2、骨钙素(BGP)、转化生长因子(TGF-β1);用生物化学的方法检测大鼠血清中碱性磷酸酶(ALK)、钙(Ca)、磷(P)和24h尿Ca、P,同时采用骨矿密度检测仪测定骨密度(BMD)。结果骨元肽结肠溶胶囊组可明显提高血清中E2、TGF-β,增加BMD,降低血清中ALK、BGP和24h尿Ca、P含量。结论骨元肽结肠溶胶囊具有提高雌激素作用,可有效抑制骨吸收,降低骨转化率,加强成骨细胞活性,增加骨密度。对去卵巢引起的大鼠骨质疏松症具有明显的防治作用。     

Efficacy of the injectable calcium phosphate ceramics suspensions containing magnesium, zinc and fluoride on the bone mineral deficiency in ovariectomized rats

The purpose of this study was to evaluate the therapeutic efficacy of a new calcium phosphate (CaP)-based formulation in improving the bone mineral deficiency in ovariectomized (OVX) rats. The ions release experiments for CaP preparations (G2: 0.46% Mg, 5.78% Zn, and 2.5% F; G3:3.1% Mg, 0.03% Zn, and 3.01% F; G4: 1.25% Mg, 1.77% Zn, 1.35% F) and of a Zn-TCP (G1: 6.17% Zn) powders, the initial Mg and Zn ion release rates of MZF-CaPs were performed in acetate buffer at pH 4.5 (37 degrees C). Wistar rats were divided into six groups including a normal (not OVX) group (GN) and a control, OVX group (GC). Rats in groups GC, G1, G2, G3, G4 were OVX. Suspensions consisting of CaP preparations (G2, G3, G4) and of a Zn-TCP (G1) powders were injected in the right thighs of OVX rats in all groups except for GN and GC, once a week for 4 weeks. GN and GC rats were injected with saline solutions. Plasma was analyzed for Zn land alkaline phosphatase levels. The bone mineral density (BMD) was measured using DEXA and the bone (femur) strength determined using three-point-bending analysis. G1 and G2 groups showed high plasma Zn levels. The area under the curve of plasma Zn was significantly greater in the G1, G2, and GN groups than in the G3, G4, and GC groups (p < 0.05). The BMD and bone mechanical strength of the right femur were significantly higher in the G1, G2, G3, and G4 groups than GC group on day 28. The right femur had significantly greater BMD and bone mechanical strength than the left femur in G1, G2, G3, and G4 groups. However, there was no significant difference in the BMD of the right femur between the G1, G2, G3, and G4 groups. Results indicate that the new injectable CaP formulations are effective in improving bone properties of OVX rats and may be useful in osteoporosis therapy.     

Calcium-level responsive controlled drug delivery from implant dosage forms to treat osteoporosis in an animal model

The effects of plasma calcium levels on estradiol release from a self-setting apatite bone cement containing 0.5% estradiol and on the bone mineral density (BMD) of ovariectomized rats were investigated. Apatite cement consisting of an equimolar mixture of tetracalcium phosphate, dicalcium phosphate dihydrate and 0.5% beta-estradiol was prepared. The in vitro release profiles from the cements in simulated body fluid containing 0, 5 and 10 mg/100 ml calcium indicated that estradiol release rate decreased with increasing calcium concentration in the dissolution medium. After subcutaneous implantation of the cement, in vivo estradiol release in diseased rats (ovariectomized rats on a low calcium diet) was significantly higher than that in normal rats. The diseased rats maintained a low calcium level during drug release. The bone mass of the recovery model rat was greater after the experiment than before. The results suggested that the severity of osteoporosis in this animals can be reduced by the implantation of this estradiol-loaded apatite cement.