Effects of catecholamines on blood pressure in the long bone marrow cavity in rats with bisphosphonate-induced osteopetrosis

Osteopetrosis is a congenital metabolic bone disease characterized by skeletal sclerosis resulting from defective osteoclast-mediated bone resorption. The disease may, inter alia, be caused by the administration of bisphosphonates (e.g. pamidronate) particularly in young humans. The issue of the effect of pamindronate-induced osteopetrosis on the function of blood circulation and autonomic nervous system remains open. In order to clarify this problem, the present study concentrated on the effect of catecholamines on blood pressure in the marrow cavity in rats with pamindronate-induced osteopetrosis. The experiments consisted in pamidronate administration to young male Wistar rats at doses of 3 mg/kg sc, for 3 or 6 weeks. Norepinephrine, epinephrine, isoprenaline as well as adrenoceptor antagonists (phentolamine and propranolol) were administered to the controls and the rats with pamindronate-induced osteopetrosis. The examinations demonstrated that rats with pamidronate-induced osteopetrosis displayed increased blood pressure in the marrow cavity. In addition, a disorder in the effect of catecholamines on blood pressure in the marrow cavity of osteopetrotic bone was observed.     

Effects of selenium dioxide on blood and femoral bone marrow of rats

This study was undertaken to investigate the effects of selenium dioxide (SeO2) on rat blood and femoral bone-marrow oxidant mechanisms. Treatment with SeO2, 67 microg Se/kg i.p. daily for 14 d, significantly decreased lipid peroxidation and the concentrations of Fe in serum and bone marrow. The concentrations of Se in serum and bone-marrow cells were significantly increased after SeO2 treatment. The activities of glutathione peroxidase (GPx) in blood and bone-marrow cells were markedly increased. The levels of oxyhemoglobin in blood were significantly increased, while the concentrations of methemoglobin were decreased after SeO2 administration. The fragility of erythrocytes membranes was significantly decreased in SeO2-treated rats compared to controls. Data suggest that treatment with a low dose of SeO2 may provide antioxidant nutrients to blood and bone marrow.     

Effect of pamidronate on the action of catecholamines on blood pressure in the marrow cavity of long bones in rats with prednisolone-induced osteoporosis

Pamidronate is a representative of bisphosphonates, which are effectively used in the treatment of bone diseases. Although a number of properties of pamidronate have been recognized which influence the metabolic process in bones, the issue of the effect of bisphosphonates on the function of blood circulation and autonomic nervous system in osteoporotic bones remains open. In order to clarify this problem, the present study concentrated on the effects of pamidronate on catecholamine action on blood pressure in the marrow cavity in rats with prednisolone-induced osteoporosis. The animals were divided into 3 groups: I - control rats; II - rats which were given prednisolone at the dose of 5 mg/kg, im, for 3 weeks; III - rats which were given prednisolone at the dose of 5 mg/kg, im and pamidronate at the dose of 3 mg/kg, sc together, for 3 weeks. The experiments demonstrated that rats with prednisolone-induced osteoporosis displayed a decreased blood pressure in the marrow cavity. In addition, a disordered action of catecholamines (norepinephrine and epinephrine) on blood pressure in the marrow cavity of osteoporotic bone was observed. Pamidronate administration in osteoporotic rats resulted in smaller increases in the blood pressure caused by norepinephrine and epinephrine in the marrow cavity of long bones.     

Influence of alpha-escin on the femoral bone strength in ovariectomized rats

The aim of the present study was to investigate the effect of alpha-escin (35 mg/kg po, daily) administered for 4 weeks on the femoral bone strength in 3-month-old ovariectomized Wistar rats. The experiments were carried out on four groups of animals: I (C)-control sham operated rats, II (OVX)-ovariectomized rats, III (E)-sham operated rats which were administered alpha-escin, IV (OVX+E)-ovariectomized rats which were administered alpha-escin. Bilateral ovariectomy caused osteopenic skeletal changes in mature female rats. alpha-Escin (35 mg/kg po, daily) administered to the ovariectomized rats for 28 days only to little extent decreased the development of osteopenic skeletal changes which were caused by bilateral ovariectomy. alpha-Escin (35 mg/kg po, daily) administered to the sham operated rats for 28 days caused slight changes in the skeletal system, which were characterized by the increase in the bone formation processes.     

奥美拉唑对去势大鼠骨密度和骨代谢的影响

目的：观察质子泵抑制剂奥美拉唑对去势雌性大鼠骨密度和骨代谢的影响,为临床合理应用质子泵抑制剂提供依据。方法：8月龄SD雌性大鼠,分成假手术组（Sham+NS组）、假手术给药组（Sham+OMZ组）、去势组（OV+NS组）、去势给药组（OV+OMZ组）。去势组大鼠行去卵巢手术建模,假手术组同等部位切除部分脂肪。给药组大鼠按体质量30 mg·kg^-1·d^-1灌胃奥美拉唑,非给药组按2 mL·d^-1生理盐水灌胃。以双能X线吸收法（DXA）检测骨密度;酶联免疫吸附法检测血清中骨代谢标志物TRAP、CTX-1、PINP、BALP、OC浓度;qRT-PCR法检测股骨骨髓细胞OPG、RANKL、c-FOS、NFATc1的mRNA表达水平以及R/O值。结果：去势组较假手术组骨密度降低、TRAP、CTX-1、PINP、OC浓度升高、R/O值升高,去势给药组较去势组骨密度降低、TRAP、CTX-1、PINP、OC浓度升高、R/O值升高。结论：质子泵抑制剂奥美拉唑可能诱导去势雌性大鼠体内的RANKL表达量相对增加,R/O值升高,进而通过OPG/RANK/RANKL信号通路使得破骨细胞活动相对增强,骨吸收代谢加快,加速骨质疏松进程。     

己烯雌酚对去卵巢大鼠骨钙、骨羟脯氨酸含量的影响

己烯雌酚对去卵巢大鼠骨丢失的防治作用 ,其骨形态计量学参数变化已有许多报道[1] ,但己烯雌酚对骨钙和骨羟脯氨酸含量的影响至今未见报道。骨钙与骨羟脯氨酸含量的比例完整体现了骨质量[2 ] ,骨钙增多而骨有机质减少 ,骨的脆性增加 ,骨质量不高。骨羟脯氨酸测定可预测骨有机质的含量[3 ] 。本研究通过对大鼠骨钙和骨羟脯氨酸含量测定 ,观察不同剂量的己烯雌酚对去卵巢大鼠骨钙、骨羟脯氨酸的影响 ,以进一步研究己烯雌酚抗骨质疏松的作用机制。1　材料与方法1.1　药品、试剂和主要仪器　己烯雌酚为广东华南制药厂的产品 ;ＷＦＸ 1Ｄ型原子吸…     

Effect of tamoxifen on bone mineral density and blood lipids in ovariectomized rats

Tamoxifen is widely used in breast cancer therapy and in the treatment of all stages of breast cancer including chemoprevention in women at high risk of the disease. The most important aspect of tamoxifen therapy concerns its influence on bone tissue and lipid metabolism. The aim of the study was to evaluate the effect of tamoxifen on bone metabolism and blood cholesterol levels in ovariectomized rats. The study was performed on Wistar rats treated with tamoxifen at 2 and 4 mg/kg/24 h. Total serum cholesterol and low density cholesterol were significantly increased in ovariectomized rats (3.24 mmol/l and 2.06 mmol/l) in comparison with sham operated control (2.68 mmol/l and 1.44 mmol/l) (p < 0.05). Total serum cholesterol and low density cholesterol in tamoxifen-treated rats were significantly decreased in comparision with the values in both sham-operated and ovariectomized control. Bone mineral content (BMC) and bone mineral density (BMD) of femurs of ovariectomized rats (0.32 g and 0.081 g/cm2) decreased significantly compared to sham-operated controls (0.42 g and 0.098 g/cm2) (p < 0.05). Tamoxifen prevented the bone mass reduction induced by ovariectomy. The treatment with tamoxifen at doses of 2 mg/kg/24 h and 4 mg/kg/24 h significantly increased BMC and BMD in comparison with ovariectomized control. The results suggest a beneficial influence of tamoxifen on bone tissue and lipid metabolism.     

Long-term effects of alendronate on fracture healing and bone remodeling of femoral shaft in ovariectomized rats

Aim:

To investigate the long-term effects of alendronate (Aln), a widely used oral bisphosphonate, on fracture healing and bone remodeling in ovariectomized rats.

Methods:

Adult female SD rats underwent ovariectomy, and then bilateral femoral osteotomy at 12 weeks post-ovariectomy. From d 2 post-ovariectomy, the animals were divided into 3 groups, and treated with Aln (3 mg·kg⁻¹·d⁻¹, po) for 28 weeks (Aln/Aln), Aln for 12 weeks and saline for 16 weeks (Aln/Saline) or saline for 28 weeks (Saline/Saline). At 6 and 16 weeks post-fracture, the fracture calluses were examined with X-ray radiography, and biomechanical testing and histological analysis were performed. The calluses were labeled with tetracycline and calcein to evaluate the mineral apposition rate (MAR).

Results:

The fracture line was less distinct in the 2 Aln-treated groups at 6 weeks post-fracture, and disappeared in all the 3 groups at 16 weeks post-fracture. The size of the callus and radiographic density of the femora in the Aln/Aln group were the highest among the 3 groups at 6 and 16 weeks post-fracture. Similar results were observed in the ultimate load at failure and energy absorption. However, the treatment with Aln delayed endochondral ossification of the callus, and significantly increased the total sagittal-sectional area, percentage callus area and callus thickness, and decreased the MAR at 6 and 16 weeks post-fracture.

Conclusion:

In the ovariectomized rat model, Aln is beneficial for the mechanical properties of the callus, but delays callus remodeling by suppressing the remodeling of woven bone into lamellar bone.     

Effects of catecholamines on the intramedullary pressure in the femur in rats with prednisolone-induced osteoporosis

Osteoporosis is a metabolic bone disease characterized by low bone mass, impaired micro-architecture and susceptibility to fracture. Osteoporosis may be, inter alia, a result of a long-term glucocorticosteroid therapy, e.g. with prednisolone. Although a number of properties of prednisolone in influencing bone metabolism have been recognized, the effect of prednisolone-induced osteoporosis on the function of blood circulation and autonomic nervous system in bones remains open. In order to clarify this problem, the present study concentrated on the effects of catecholamines on intramedullary pressure in rats with prednisolone-induced osteoporosis. Prednisolone was administered to male Wistar rats at the doses of 5 mg/kg im, for 3 weeks. Norepinephrine, epinephrine, isoprenaline as well as adrenoceptor antagonists (phentolamine and propranolol) were administered to the controls and to the rats with prednisolone-induced osteoporosis. The examinations demonstrated that rats with prednisolone-induced osteoporosis displayed a decreased intramedullary pressure. In addition, a disordered effect of catecholamines on intramedullary pressure of osteoporotic bone was observed.     

Effects of phenylhydrazine or phlebotomy on peripheral blood, bone marrow and erythropoietin in Wistar rats

This study was conducted to characterize better the response of rats to blood loss and hemolysis and to incorporate automated methods into the routine evaluations of those responses. Serial phlebotomies of 1.5-2.0 ml of blood per day for 5 days, or intraperitoneal injection of 50 mg kg(-1) phenylhydrazine (PHZ) for 3 days, were used to cause anemia associated with blood loss or hemolysis, respectively. Maximum decreases in red blood counts were observed on Day 3 in PHZ-treated animals (68%) and Day 4 in blood-loss animals (35%). In the routine complete blood count (CBC), hemoglobin, hematocrit/hemoglobin ratio and erythrocyte indices could be used to discriminate between the two treatments. Free plasma hemoglobin in PHZ-treated animals resulted in marked elevations of mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) with a 2:1 hematocrit/hemoglobin ratio rather than the anticipated 3:1 ratio. Although both groups of animals had elevated white blood cell counts, PHZ-treated animals also had monocytosis and basophilia. Reticulocyte counts were more sensitive than erythropoietin (EPO) concentrations in predicting erythroid changes. Maximum mean reticulocyte values were ca. 24% in serially phlebotomized animals and >99% in PHZ-treated rats. Plasma EPO levels were 4-10-fold higher than EPO levels in urine, kidney or liver. Flow cytometric differentials of rat bone marrow using 2, 7-dichlorofluorescin successfully predicted erythroid hyperplasia in both experimental groups. Erythrocyte indices returned to normal within 14 days and the remaining CBC parameters were normal within 28 days for both treatment groups. Reticulocyte counts remained slightly elevated on Day 28, but were normal when assessed at Day 56 in blood-loss and PHZ-treated animals.     

鹿龟生骨丸对去卵巢大鼠骨代谢生化指标的影响

目的:研究鹿龟生骨丸对去卵巢大鼠骨代谢生化指标的影响,探讨鹿龟生骨丸治疗骨质疏松的作用机制。方法:采用去卵巢大鼠模型,分模型对照组、假手术组、鹿龟生骨丸组、雌激素对照组。去势1个月后鹿龟生骨丸组、雌激素对照组服药10周,放免法测定血清雌二醇(E2)、骨钙素(OC)、速率法测定血清碱性磷酸酯酶(ALP)及抗酒石酸酸性磷酸酶(TRACP),组间进行比较。结果:E2测定,用药后鹿龟生骨丸组、雌激素对照组E2水平均高于模型对照组,且都有极显著性(P<0.01)。雌激素对照组高于鹿龟生骨丸组,差异有显著性(P<0.05);OC测定,鹿龟生骨丸组、雌激素对照组均低于模型对照组,有显著性(P<0.05);ALP测定,鹿龟生骨丸组、雌激素对照组均低于模型对照组,有显著性(P<0.05);TRACP测定,用药后TRACP水平均下降,但雌激素对照组下降水平更接近假手术组,鹿龟生骨丸组与雌激素对照组相比无显著性(P>0.05)。结论:鹿龟生骨丸对绝经后骨质疏松有增加E2、促进骨形成、抑制骨吸收的作用。     

Effects of chronic beta-adrenoceptor antagonism on plasma catecholamines and blood pressure in hypertension

Plasma catecholamines were measured before and after treatment with beta-adrenoceptor antagonists in 17 hypertensive patients. Chronic treatment with beta-adrenoceptor antagonists caused substantial reductions in heart rate and intra-arterial blood pressure recorded continuously during ambulation. Before treatment, a quantitative relationship was observed between plasma norepinephrine and blood pressure and heart rate during a variety of activities; a similar relationship was also observed after chronic treatment five of six patients, suggesting that plasma norepinephrine remains an index of sympathetic activity despite the influence of beta-adrenoceptor antagonism. After treatment, plasma norepinephrine tended to be higher at any level of blood pressure, although not significantly so. Chronic treatment caused no significant change in mean resting plasma levels of norepinephrine and epinephrine. During exercise, plasma norepinephrine and epinephrine levels were significantly elevated above control after acute but not after chronic treatment. These observations do not support the hypothesis that beta-adrenoceptor antagonist drugs lower blood pressure in hypertensive man through a sympatholytic mechanism in he central nervous system or at peripheral presynaptic receptors.     

依普拉芬对去卵巢大鼠骨力学性能的影响

目的研究依普拉芬对去卵巢大鼠骨密度和骨生物力学指标变化的影响。方法腹腔手术切除大鼠双侧卯巢,分为阴性对照组,依普拉芬低、中、高剂量组和雌激素对照组,另设一假手术组,分别给予基础饲料和不同剂量受试物,12周后进行骨密度和生物力学测定。结果大鼠去卵巢后骨密度显著下降,股骨的力学性能指标有较大变化。给予依普拉芬后,可使骨密度显著提高,存在一定的剂量-效应关系,弯曲强度和弯曲弹性模量明显增加,但其作用均高于雌激素对照组,差异均有统计学意义（P〈0．01和P〈0．05）。结论依普拉芬可增加去卵巢大鼠股骨骨密度、改善部分骨生物力学性能。     

联合应用特乐定与固邦对去卵巢大鼠骨骼作用研究

目的　观察特乐定与固邦联合用药是否对大鼠骨骼产生增强疗效的作用。方法　 3mon龄♀SD大鼠 4 2只 ,体重 (2 6 6± 2 2 ) g ,随机分为 6组 ,除了第 1组实行Sham手术外 ,其余 5组均实行去卵巢 (Ovx)手术。Sham大鼠给予蒸馏水 ,各Ovx大鼠分别给予蒸馏水、1mg·kg-1·d-1固邦、2 70mg·kg-1·d-1的葡萄糖酸钙、5 6mg·kg-1·d-1的特乐定及结合 1mg·kg-1·d-1固邦与 5 6mg·kg-1·d-1的特乐定。实验期限为 3mon ,处死前注射荧光标记。实验结束后取左侧胫骨近心端 ,行骨组织形态计量学分析。结果　固邦增加大鼠骨量 ,抑制去卵巢大鼠的骨形成指标 (%L .Pm ,BFR/BS)和骨吸收指标 (N .Oc/Tb .Pm)。单独补充葡萄糖酸钙未能缓解Ovx大鼠的骨量丢失。特乐定亦未能有效恢复Ovx大鼠丢失的骨量。固邦与特乐定联合用药虽然增加去卵巢大鼠的骨量 ,但其骨量不比单用固邦的骨量高。结论　固邦与特乐定的联合应用 ,不能发生疗效增强的效果 ,不推荐两药同时使用     

槲皮素对去卵巢大鼠生殖系统及骨密度的影响

目的探讨槲皮素在体内的雌激素样作用。方法健康雌性SD大鼠48只按体重随机分为6组：假手术组（SHAM）、单纯去卵巢组（OVX）、17β-雌二醇组[ERT，0．1mg／（kg·d）]、高剂量槲皮素组[QH，300mg／（kg·d）]、中剂量槲皮素组[QM，150mg／（kg·d）]、低剂量槲皮素组[QL，75mg／（kg·d）]。除假手术组外其余各组均切除双侧卵巢，术后1周开始给药，连续16周。给药期间每天观察阴道脱落细胞涂片。处死大鼠后，测量子宫重量计算子宫系数，病理切片观察子宫内膜及腺体，测量腰椎和股骨骨密度。结果槲皮素能使去卵巢大鼠阴道上皮细胞角化、子宫系数增加、腺体及内膜增生，骨密度增加（P〈0．05）。结论槲皮素在去卵巢大鼠体内具有弱雌激素样作用，能减轻雌激素缺乏导致的生殖系统萎缩，且能防止骨量丢失。     

大豆异黄酮对去卵巢大鼠骨密度和雌激素活性的影响(英文)

目的 :研究大豆异黄酮对去卵巢大鼠骨密度以及雌激素活性的影响。方法 :将 10～ 12月龄的雌性Wistar大鼠随机分为 6组 :假手术组 (SHAM )、切卵巢模型组 (OVX)、尼尔雌醇组 (OVX E)、小剂量异黄酮组 (L ISO)、中剂量异黄酮组 (M ISO)、大剂量异黄酮组 (H ISO) ,每组 8只。后 5组大鼠被切除双侧卵巢 ,SHAM组只被切除卵巢附近脂肪组织。L ISO ,M ISO ,H ISO分别灌胃给予 30 ,6 0 ,12 0mg·kg- 1的大豆异黄酮 ,OVX E组大鼠灌胃给予0 .2mg·kg- 1·wk- 1的尼尔雌醇 ,SHAM与OVX组以等剂量的溶剂灌胃 ,15wk后股动脉放血处死动物 ,收集血液用于血清碱性磷酸酶活性、血清雌二醇水平、血钙、血磷测定 ,分离出右侧股骨、第 2腰椎用于骨密度测量 ,测定双侧子宫重量。结果 :与SHAM组相比 ,OVX组股骨骨密度和椎骨骨密度均可见不同程度降低 (P <0 .0 5和P >0 .0 5 ) ,尼尔雌醇与异黄酮 12 0mg·kg- 1能明显升高去卵巢大鼠的股骨和椎骨骨密度 (P <0 .0 5 )。OVX组的血清碱性磷酸酶水平高于SHAM组 (P <0 .0 5 ) ,异黄酮6 0mg·kg- 1可降低去卵巢大鼠的血清碱性磷酸酶水平 (P <0 .0 5 )。OVX组的血清雌二醇水平与子宫系数明显低于SHAM组 (P <0 .0 1) ,异黄酮的不同剂量组与OVX E组的血清雌二醇水平、子宫系数都明显高于OV     

Oxidative effects of nickel on bone marrow and blood of rats

This study was undertaken to examine the oxidative effects of nickel (Ni) on rat blood and bone marrow. Treatment with either 100, 250, or 500 micromol/kg Ni i.p. significantly enhanced lipid peroxidation in serum and bone marrow after 24 h. The concentrations of Ni and Fe in serum and bone marrow cells were also significantly increased after NiCl2 administration. After treatment with NiCl2, the activities of glutathione peroxidase (GPx) and levels of alpha-tocopherol in bone marrow cells were markedly reduced. There was an inverse association thiobarbituric acid elevated (TBA)-chromogen product with decreased GPx activity and alpha-tocopherol levels in bone marrow cells of NiCl2-treated rats. The concentrations of alpha-tocopherol in blood significant reduced with 100 and 250 micromol/kg Ni but returned to control at the 500-micromol/kg dose. Data suggest that lipid peroxidation may be a contributing factor in Ni-induced tissue oxidative stress.     

葛根提取物对去卵巢大鼠血液指标的影响

目的研究葛根提取物对去卵巢大鼠血液指标的影响,探讨葛根提取物治疗骨质疏松的药理作用。方法将120只成年雌性大鼠随机分成6组,采用去卵巢大鼠模型,分为葛根提取物剂量组(高、中、低剂量),同时设立假手术组、去卵巢对照组和雌激素对照组。手术1个月后给药,连续给药3个月,末次给药后,禁食24h,所有动物眶静脉取血,测定血清雌二醇(E2)、骨钙素(BGP)、血钙、血磷、血清碱性磷酸酶(ALP)、血清抗酒石酸酸性磷酸酶的含量。结果大鼠去卵巢后,血清雌二醇减少,骨钙素水平升高,血钙、血磷水平均降低,血清碱性磷酸酶和抗酒石酸酸性磷酸酶含量增加。结论葛根提取物可改善去卵巢大鼠的血液生化、免疫学指标,具有对抗去卵巢导致的骨质疏松的作用。     

Policosanol prevents bone loss in ovariectomized rats

Osteoporosis is characterized by reduced bone mass, abnormal bone architecture and increased fracture risk. Ovariectomy impairs bone mass and metabolism in rats and ovariectomized rats are considered as a suitable model of postmenopausal osteoporosis. Mevalonate is required for producing lipoids that are important in osteoclast activity and thus drugs affecting mevalonate production can prevent bone loss in rodents. Policosanol is a cholesterol-lowering drug isolated from sugar cane wax that inhibits cholesterol biosynthesis through an indirect regulation of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity. The purpose of this study was to determine whether policosanol could prevent bone loss in the bones of ovariectomized rats by comparing its effects with those induced by estradiol. Sprague Dawley female rats were randomly distributed in four groups: a sham-operated group treated with Tween/H2O vehicle and three groups of ovariectomized rats treated with 17beta-estradiol (30 microg/kg/day) or policosanol (50 and 200 mg/kg/day), respectively, for 3 months. At treatment completion the rats were sacrificed, their bones removed and variables of bone resorption and formation were investigated by histomorphometry. Ovariectomy increased trabecular separation but diminished the number and thickness of trabecules. Estradiol and policosanol prevented these effects compared with ovariectomized controls. Both treatments also prevented an increase in the number of osteoclasts and their surface area induced by ovariectomy. Estradiol, but not policosanol, significantly prevented an increase of osteoblast surface area compared with ovariectomized controls. In conclusion, policosanol prevented bone loss and decreased bone resorption in ovariectomized rats, suggesting that it should be potentially useful in preventing bone loss in postmenopausal women.