RGDY对去势大鼠骨密度和骨形态计量学的影响

The effects of RGDY on bone mineral density and histomorphometry in OVX rats

目的探讨抗骨质疏松新药四环素-RGDY对去势SD大鼠骨代谢的影响及其各项参数间的相关关系。方法 4月龄雌性SD大鼠54只随机分为6组:假手术组(S),双侧卵巢切除术(OVX)组(O)、阿伦膦酸钠组(A)、四环素组(T)、RGDY组(R)、四环素-RGDY组(TR)。S组行假手术,其余各组行OVX,术后次日S、O组每日皮下注射磷酸盐缓冲液(PBS),A、T、R、TR分别按体质量每日皮下给予阿伦膦酸钠、四环素、RGDY、四环素-RGDY PBS溶液,连续给药9周,测定各组大鼠骨密度,取近端胫骨干骺端行骨计量学测定。结果干预9周后S组体质量显著低于其他各组,子宫质量/体质量比值高于其他各组。A组股骨全段、远端干骺端、腰椎L_(1～4)3个部位的骨密度及股骨灰重/干重比值(AW/DW)均显著高于O组,TR组AW/DW显著高于O组。TR组骨小梁体积/骨小梁面积(TBV/TTV)、骨小梁体积/海绵骨体积(TBV/SBV)、平均骨小梁板密度(MTPT)均较O组显著增加,骨小梁面积/体积比(S/V)及MTPS较O组分别下降。TR组四环素单标记表面占骨小梁表面的百分比[Sfract(s)]、四环素双标记表面占骨小梁表面的百分比[Sfract(d)]分别较O组下降,四环素双标记线间的平均距离(DDL)、骨矿化沉积率(MiAR)分别较O组增加。TR组DDL、MiAR显著高于R组,而Sfract(s)显著低于T组。相关分析提示骨计量参数TBV、MTPT与股骨远端干骺端BMD值之间呈显著正相关(r_1=0.687,P<0.05;r_2=0.782,P<0.05)。结论四环素-RGDY可改善干骺端骨小梁的连接性,有效预防大鼠去势后的快速骨丢失。

Objective To evaluate the effect of the new anti-osteoporotic drug Tc RGDY on prevention against bone loss in ovariectomized rats and explore the relationships between bone mineral density and histomorphometric parameters. Methods Fifty four female SD rats were divided into six groups by body weight randomly： shamed operated group （S）, ovariectomized group （0）, alendronate therapy group （A）, Tc therapy group （T）, RGDY therapy group （R）, Tc-RGDY therapy group （TR）. Subcutaneous administration of alendronate, Tc, RGDY,Tc-RGDY were initiated separately on A, T,R, TR group and simultaneously rats of S and O group were given phosphate buffered saline every day for nine weeks. The BMD of whole femur, distal femur metaphysis and L1-4 were measured by dual energy X ray absorptiometry, while histomor- phometry of proximal tibia were performed. Results A significant increase of AVC/DW was revealed in TR group as compared with the O, R, T group, but there was only an increased trend of BMD on the three sites of bone in TR group. Histomorpho- metry in the TR group, parameters of the TBV/TTV, TBV/SBV, and MTPT were statistically increased and parameters of MTPS, S/V decreased as compared with O group. Compared with O group, Sfract （s）, Sfract （d） in TR group significantly decreased; DDL significantly increased. Correlation analysis showed that TBV, MTPT were significantly positively related with BMD value of femur distal metaphysic（ r 1 =0.687, P 〈0.05; r2 =0.782, P 〈0.05）. Conclusion The Tc-RGDY could effectively prevent rapid bone loss in ovariectomized rats while the connectivity of trabecular bone could be significantly im- proved.