【摘要】 目的用现代药理学技术研究3个暴露剂量的受试品JGYS对骨重、骨密度、骨钙及骨代谢的影响,评价JGYS受试品对去卵巢大鼠骨质疏松症的治疗作用及其剂量-效应关系.方法 （1）摘除6月龄雌性大鼠双侧卵巢,复制高转换型骨质疏松症模型.假手术和模型动物进行以下分组,10只/组,即（1）假手术组（未摘除卵巢）;（2）去卵巢模型组;（3）去卵巢模型动物+300 mg/kg低剂量JGYS组;（4）去卵巢模型动物+600mg/kg中剂量JGYS组;（5）去卵巢模型动物+1 200 mg/kg高剂量JGYS组;（6）去卵巢模型动物+500 mg/kg仙灵骨葆胶囊阳性药物对照组;（7）去卵巢模型动物+0.03 mg/kg己烯雌酚阳性对照组.受试品（JGYS药料）、阳性对照品（仙灵骨葆胶囊药料和粉碎的己烯雌酚片）均悬浮于0.5%羧甲基纤维素钠中.假手术组和去卵巢模型组动物按1 m L/100 g体重灌胃0.5%羧甲基纤维素钠,1次/d,连续90 d.（3）⁵组灌胃给予受试品药液,灌胃体积均为1 m L/100 g体重、1次/d、连续90 d.阳性对照品均以1 m L/100 g体重灌胃给药,1次/d,连续90d.末次给药后取血制备血清,检测血清碱性磷酸酶（alkaline phosphatase,ALP）、抗酒石酸酸性磷酸酶（tartrate-resistant acid phosphatase,TRAP）、血清钙和血清磷水平,牺牲动物后检测子宫指数;双能X线检测股骨和腰椎的骨密度和骨矿含量;原子吸收方法测定股骨和椎骨的骨钙含量.结果 （1）对子宫指数的影响:与模型组比较,1 200 mg/kg JGYS可明显降低大鼠的体重,升高其子宫指数,600 mg/kg JGYS降低体重,增加子宫指数,300 mg/kg JGYS对大鼠的体重和子宫指数均无明显影响.600 mg/kg JGYS对子宫指数的影响与仙灵骨葆胶囊相当,但明显弱于己烯雌酚片.（2）对骨代谢指标的影响:与模型组比较,600和1 200 mg/kg的JGYS明显降低ALP和TRAP的活性,300 mg/kg JGYS对ALP和TRAP活性均无明显影响.600 mg/kg JGYS对ALP和TRAP的作用与仙灵骨葆胶囊及己烯雌酚相当.与去势模型组比较,3种剂量的JGYS对血钙、血磷水平均无明显影响.（3）对骨量的影响:对股骨骨密度和骨矿含量的影响:与模型组比较,600、1 200 mg/kg的JGYS明显增加股骨的骨密度和骨矿;300 mg/kg的JGYS对股骨的骨密度和骨矿均无明显影响.600 mg/kg JGYS增加股骨骨密度及骨矿的作用与500 mg/kg仙灵骨葆胶囊及0.03 mg/kg己烯雌酚相当.对椎骨骨密度和骨矿含量的影响:3种剂量的JGYS明显增加椎骨的骨密度和骨矿含量.300¹ 200 mg/kg的JGYS增加椎骨的骨密度和骨矿含量的作用与500 mg/kg的仙灵骨葆胶囊相当;1 200 mg/kg的JGYS增加椎骨的骨密度作用强于仙灵骨葆胶囊.对骨湿重、干重、灰重和骨钙含量的影响:与模型组比较,600和1 200 mg/kg JGYS均明显增加股骨和椎骨的骨钙含量,并提高湿重、干重和灰重;300 mg/kg JGYS对股骨的上述指标无明显影响,但增加椎骨的骨钙和骨重.600 mg/kg JGYS的作用与500mg/kg仙灵骨葆胶囊相当,但弱于0.03 mg/kg的己烯雌酚.结论在高转换型骨质疏松症模型中,JGYS具有调节骨代谢、增加骨量和骨密度作用.更多还原

【Abstract】 Objective To study the effects of JGYS on bone weight, bone mineral density, and bone calcium, and to evaluate the therapeutic effects on ovariectomy(OVX)-induced rat osteoporosis and its dose-effect relationship. Methods Female Sprague-dawly(SD) rats were randomly divided into an ovariectomized(OVX) group and a sham operation group. The rats in OVX group were ovariectomized. However, for the rats in sham group,only a part of fat near both ovaries were removed under the same anesthesia and surgical approach. Bone mineral density, mechanical properties, and serum biochemical parameters were examined 90 d after OVX to characterize the experimental animal model. After osteoporotic rat model establishment, rats in OVX group were divided into model group,diethylstilbestrol group,300 mg/kg,600 mg/kg,1 200 mg/kg JGYS groups,and 500mg/kg Xianlingubao capsule,ten rats in each group. All the above drugs were administered orally for 90 d. Bone mineral density and serum biochemical parameters were examined respectively by dual-energy X-ray absorptiometry analysis and enzyme-linked immunoassay. Results(1) Effect on the uterus index: compared with model group,1200 mg/kg JGYS could obviously reduce the weight of rats, and increase the uterus index; 600 mg/kg JGYS reduced weight and increased the uterus index;300 mg/kg JGYS had no significant effect on rat weight and the uterus index; the effect on the uterus index of 600 mg/kg JGYS was similar to Xianlingubao capsule, but significantly weaker than diethylstilbestrol.(2) Effect on bone metabolism index: 1 the effect on serum ALP,TRAP: compared with the model group, 600 and 1200 mg/kg JGYS could significantly decrease the activity of ALP and TRAP, 300 mg/kg JGYS had no obvious effect on the activity of ALP and TRAP. The function of 600 mg/kg JGYS was similar to Xianlingubao capsule and diethylstilbestrol. 2 the effect on the blood calcium and blood phosphorus: compared with OVX group, three doses of JGYS showed no significant effect either on blood calcium or on blood phosphorus levels.(3) Effect on bone mass: 1 the effect on femoral bone mineral density and bone mineral content: compared with the model group, 600-1200 mg/kg JGYS groups could significantly increase femoral bone mineral density and bone mineral content;300 mg/kg JGYS showed no significant effect.The effect of increasing femoral bone mineral density and bone mineral content for 600 mg/kg JGYS was same as 500 mg/kg Xianlingubao capsule and 0.03 mg/kg diethylstilbestrol. 2 the effect of vertebral bone mineral density and bone mineral content :three doses of Yishenjiangu tablet obviously increased vertebral bone mineral density and bone mineral content. The effect on increasing the vertebral bone mineral density and bone mineral content was similar to 500 mg/kg Xianlingubao capsule; the 1200 mg/kg JGYS tablet’s function for increasing vertebral bone mineral density was better than Xianlingubao capsule. 3the effect on wet,dry,and ash weight of bone and bone calcium content: compared with the model group, 600 and 1200 mg/kg JGYS significantly increased femoral and vertebral bone calcium content, and increased the content of wet,dry weight and ash weight; 300 mg/kg JGYS had no significant effect on the former index, but increase the calcium and bone of vertebral bone. The function of 600 mg/kg JGYS was similar to 500 mg/kg Xianlingubao capsule, but weaker than 0.03 mg/kg diethylstilbestrol. Conclusion JGYS can modulate bone metabolism and increase bone mass,and shows a therapeutic effect on OVX-induced rat osteoporosis in a dose- effect manner.更多还原