依替膦酸二钠对骨质疏松症模型大鼠股骨节段性骨缺损修复的影响及靶基因的探索
Effect of etidronate disodium on the restoration of segmental bone defects of the femur in osteoporotic rats and the target gene exploration
  
DOI:10. 3969/j. issn. 1006-7108. 2012. 12. 001
中文关键词:  骨质疏松症  节段性骨缺损  依替膦酸二钠  OPG
英文关键词:Osteoporosis  Segmental bone defect  Etidronate disodium  OPG
基金项目:
作者单位
徐晓峰 陈海宁 陈琛 陈亮 赵镒汶 刘自文 212000镇江江苏大学附属医院 
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中文摘要:
      目的①观察依替膦酸二钠对骨质疏松症大鼠骨缺损修复的影响。②探求双膦酸盐类药物影响骨质疏松症大鼠骨缺损修复的靶基因。方法 取6月龄雌性SD大鼠60只,随机选取20只加入空白对照组(N组),余下40只药物干预组(D组)、模型组(M组)。D组、M组予建立骨质疏松症模型,N组予行假手术。首次造模成功后饲养3个月,然后3组均建立节段性骨缺损模型。药物组每周给予依替膦酸二钠(4.0 mg/kg)肌注1次;模型组和空白组每周给予同体积生理盐水肌注1次。在骨缺损模型建立后第2、4、6、8周建立4个观察时间点,分别观察:①骨缺损断端影像学(DR)表现;②骨缺损区组织学改变;③骨缺损区域骨痂中OPG的基因表达。结果 在骨缺损愈合过程中,DR表现及组织学改变示:N组最好,M组最差,D组愈合介于两者之间并偏向于N组。OPG基因的表达随时间变化而增加,各组趋势与上述改变基本一致。结论 依替膦酸二钠作为双膦酸盐类药物的代表对骨质疏松症大鼠节段性骨缺损的修复有促进作用,OPG基因可能是其作用位点。
英文摘要:
      Objective To observe the effect of etidronate disodium on bone defect restoration in osteoporotic rats,and to explore the target gene related to this mechanism. Methods A total of 60 6-month female SD rats were selected. They were divided into 3 groups randomly ( n =20 ), blank control group ( Group N ), drug intervention group ( Group D ), and model group ( Group M ). Rats in Group D and Group M were treated to build osteoporotic model,meanwhile rats in Group N received sham operation. All the rats were fed for 3 months after first successful modeling. Segmental bone defect model was established in rats in all the 3 groups. Rats in Group D received an intramuscular injection of etidronate disodium ( 4. 0 mg/kg ) once a week,while rats in Group N and Group M were injected with same volume of normal saline instead. Four observation time points were established on the 2nd,4th, 6th, and 8th week after bone defect modeling.Imaging (DR ),histologic changes,and OPG gene expression of bone defect regions were observed. Results During the healing process of bone defects,DR and histologic changes showed that the healing was the best in Group N, the worst in Group M,in the middle but similar to Group N in Group D. The expression of OPG gene increased along with time,and the trend in all 3 groups was in coincident with the changes above.Conclusion As the representative of bisphosphonate drugs, etidronate disodium promotes the restoration of segmental bone defects of the femur in osteoporotic rats. OPG gene may be the target site of its action.
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