不同剂量蛇床子素对OPG基因敲除小鼠和去卵巢骨质疏松大鼠作用疗效的比较研究  

Comparison study of the effect of different doses of osthole on OPG knockout mice and OVX rats

作　　者：赵永见[1] 唐德志[2] 程少丹 郑为超[1] 施杞[2] 王拥军[2] 

机构地区：[1]安徽理工大学医学院,安徽淮南232001 [2]上海中医药大学脊柱病研究所,上海200032 [3]上海市光华中西医结合医院,上海200052

出　　处：《中国骨质疏松杂志》2015年第2期147-151,共5页Chinese Journal of Osteoporosis

基　　金：教育部创新团队发展计划项目(IRT1270);国家自然科学基金青年基金(81102604);上海市卫生系统新优青培养计划项目(XYQ2013085);上海高校实验技术队伍建设计划项目(lh0124001)

摘　　要：目的观察不同剂量蛇床子素对OPG基因敲除小鼠和去卵巢骨质疏松大鼠的影响。方法选择3种不同剂量的蛇床子素作用于OPG基因敲除小鼠和去卵巢骨质疏松大鼠,以双能X骨密度仪检测动物全身骨密度的变化;将动物腰椎做硬组织切片,并进行骨形态计量学分析其骨小梁的变化。结果对于OPG基因敲除小鼠,蛇床子素能提高其全身BMD,以中剂量(10 mg/(kg·d))组提高最为明显,低剂量(5 mg/(kg·d))次之,而高剂量(15 mg/(kg·d))组效果最差。蛇床子素能提高OPG基因敲除小鼠腰椎骨小梁体积分数,增加骨小梁数目,增加骨小梁厚度,降低骨小梁分离度,其中以5 mg/(kg·d)组作用最明显,其次为10 mg/(kg·d)组,而15 mg/(kg·d)组则效果最差;对于去卵巢骨质疏松大鼠,不同剂量的蛇床子素均能显著提高大鼠全身BMD,其中以中剂量(100 mg/(kg·d))组为最佳。蛇床子素能显著提高大鼠腰椎骨小梁体积分数,以100 mg/(kg·d)组最明显。显著增加大鼠腰椎骨小梁数目,以75 mg/(kg·d)组最明显。蛇床子素100 mg/(kg·d)组能增加大鼠腰椎骨小梁厚度。不同剂量的蛇床子素均能显著降低大鼠腰椎骨小梁分离度,其中以75 mg/(kg·d)组和100 mg/(kg·d)组最明显。结论蛇床子素能促进骨形成,抑制骨吸收,从而起到抗骨质疏松的作用,其疗效与给药剂量密切相关。Objective To observe the therapeutic effect of osthole with different doses on OPG knockout mice and ovariectomyinduced osteoporotic rats.Methods Three doses of osthole were used to treat OPG knockout mice and ovariectomized rats.BMD of the total body was measured using dual energy X-ray absorptiometry（DXA）.The lumbar vertebrae were sliced without decacification and histomorphometric analysis was performed.Results In OPG knockout mice,osthole increased BMD of the total body.The effect with the middle dose（10 mg/（kgd）） of osthole was the most significant,then the low dose（5 mg/（kg·d）） and the high dose（15 mg/（kg ·d））.Osthole increased the volume ratio,number,thickness,and the separation of the trabeculae.The effect with the low dose was the most significant,then the middle and the high dose.In OVX rats,osthole of all the doses increased BMD of the total body.The effect with the middle dose（100 mg/（kg·d）） of osthole was the most significant.Osthole significantly increased the volume score of the trabeculae with a dose of 100 mg/（kg·d）.Osthole significantly increased the number of the trabeculae with a dose of 75 mg/（kg·d）.Osthole significantly increased the thickness of the trabeculae with a dose of100 mg/（kg·d）.Different doses of osthole decreased the separation of the trabeculae,and the most effect achieved with the doses of 75 mg/（kg·d） and 100 mg/（kg·d）.Conclusion Osthole can enhance bone formation and inhibit bone resorption.Its antiosteoporosis effect is closely associated with the dose of the drug.

关 键 词：蛇床子素 骨质疏松 去卵巢 OPG基因敲除 剂量 对比研究 

分 类 号：R965[医药卫生—药理学]