辛伐他汀间断给药对去卵巢大鼠成骨作用的初步实验观察  

Stimulation of bone formation in ovariectomized rat by intermittent administration of simvastatin

作　　者：叶伟胜[1] 于顺禄[2] 马宝通[1] 李健兵[2] 

机构地区：[1]天津市天津医院创伤骨科,300211 [2]天津市天津医院骨科研究所,300211

出　　处：《中华骨科杂志》2001年第7期428-432,共5页Chinese Journal of Orthopaedics

摘　　要：目的了解辛伐他汀间断给药对骨形成的作用。方法70只SD雌性大鼠,随机分为去卵巢手术组实验组,50只和假手术组对照组,20只,术后30d,两组各处死10只动物,以确立骨质疏松动物模型制备成功。假手术组另10只动物作为正常对照组A组。实验组40只动物重新分为4组,每组各10只动物单纯去卵巢组B组;雌激素组阳性对照组C组,给予尼尔雌醇0.1mg/kg·d;钙制剂组D组,给予碳酸钙10mg+维生素D32IU/kg·d辛伐他汀组E组,服用辛伐他汀5mg/kg·d,连续给药14d,停用28d再给药14d。于术后30d通过胃肠灌注给药,3个月后取材进行骨密度测量和骨计量学测定。结果E组动物服用辛伐他汀后,骨矿含量(46±11.34)mg和骨密度值(41.8±8.38)mg/cm2明显高于B组(34±5.16mg、31.6±7.04)mg/cm2和D组P<0.05但B、D两组比较差异无显著性意义P>0.05。骨组织计量学结果显示,E组骨体积(52.18%±3.42%)、类骨质表面(44.16%±3.99%)、骨重建时间(9.91±1.09d均高于B组P<0.01;同时骨吸收表面明显增加(30.62%±3.32%,P<0.01)。结论辛伐他汀间断给药具有刺激骨形成作用,但同时也有明显的促进骨质吸收作用。Objective To study the effect on bone formation by intermittent administration of simvastatin. Methods Seventy three month old virgin female rats, weighted (200±10) g each had been divided into two groups ovariectomized (50 rats) and pseudo ovarectomized (20 rats). Ten rats each of Group A and Group B were sacrified at the 30 th day for the confirmation of successful establishment models of the osteoporosis. Then the remaining animals were re divided into 5 groups: Group A, pseudo ovarectomized control, 10 rats; Group B, ovarectomized control, 10 rats; Group C, given Nylestriol 0.1 mg/(kg·d), 10 rats; Group D, 10 rats, given calcium 10 mg and vitamin D3 2 IU/(kg·d); Group E, 10 rats given simvastatin 5 mg/(kg·d) for 14 days; and the drug was suspended for 28 days, then simvastatin was given for another 14 days. All of the animals were given the agents through gastric tube 30 days after surgery. At 120 th day all the rats were sacrified for the measurements of bone mineral content and bone mineral density by the dual energy X ray absorptiometry for bone mophometrical study. Results The average of bone mineral content was (46±11.34) mg (P< 0.05) and bone mineral density (41.80±8.38)mg/cm2 in the right femur of Group E which were significantly higher than that of Group B and D (P< 0.01), and similar to Group C. In the bone morphometrical study the average of bone volume was 52.18%±3.42%(P< 0.01), osteoid surface 44.16%±3.99%, (P< 0.01) and bone remodeling time (9.91±1.09) d (P< 0.01), the parameters were also significantly higher than that of Group B, while simultaneously the bone absorption surface were significantly larger (30.62%±3.32%,P< 0.01) than that of Group B. Conclusion Intermittent administration of simvastatin could stimulate bone formation, while at same time it also increased bone absorption.

关 键 词：卵巢切除术 骨质疏松 绝经 酶类 辅酶 酶抑制剂 动物替代试验 骨组织形态 他汀类药物 

分 类 号：R68[医药卫生—骨科学]