成骨生长肽羧基端5肽衍生物G48A和阿仑膦酸钠的序贯治疗对去卵巢大鼠的影响

Sequential therapy with osteogenic growth peptide C-terminal pentapeptide derivative G48A in ovariectomized rats

目的探讨成骨生长肽羧基端5肽衍生物G48A与阿仑膦酸钠（A len）的序贯治疗对去卵巢（OVX）大鼠离体骨密度和生物力学的影响。方法将3月龄雌性SD大鼠75只随机分7组,除假手术组（S组）外均行OVX术,1周后G48A1、G48A2、G48A3组分别以5-5-5 d、10-10-5 d、14-14-7 d为周期交替给予G48A-（A len）-间歇进行预防治疗;NADFR组每日联合予G48A和A len;ALEN组每日予A len;余OVX组和S组每日予安慰剂。术后13周处死,分离左股骨及1~4腰椎行骨密度（BMD）检测,右股骨行三点弯曲实验,第5腰椎行腰椎压缩实验。结果与S组比较,OVX组体质量增加,BMD明显降低,腰椎最大载荷、比例极限、强度极限和弹性模量以及股骨的弯曲能量明显减低;经过G48A1、2、3组及NADFR组预防性治疗,各项指标绝大多数有改善趋势,其中腰椎和股骨BMD、腰椎弹性载荷以及股骨的弯曲弹性模量和弯曲刚性系数均较OVX组有显著提高。结论G48A与阿仑膦酸钠的序贯治疗可以改善去卵巢大鼠的骨丢失,增加骨密度,提高骨力学性能。

Objective To study the effects of G48A and alendronate in activation-depression-free-repeat（ADFR） scheme on ovariectomized rats.Methods Seventy-five female Sprague-Dawley rats were randomly divided into 7 groups： sham-operated（S） group,ovariectomized（OVX）group,alendronate group（Alen）,G48A and alendronate group（non-ADFR group）,and the other three groups were treated by ADFR scheme with G48A and alendronate given intermittently by different time schedule：5-5-5 d（group G48A1）,10-10-5 d（group G48A2）,14-4-7 d（group G48A3）.All rats were sacrificed 13 weeks after the operation.The BMD of femora and lumbar vertebra and the biomechanical parameters were measured.Results Body weight increased and BMD decreased in OVX compared those with S group.The lumb and vertebral BMD,the vertebral elastic load,the femoral flexural modulus and flexural rigidy coefficient in groups G48A1,2,3 and non ADFR group were significantly increased as compared withthose in group OVX.The BMDs of ADFR groups and non-ADFR group did not have significant difference compared with S group.Conclusion The bone loss is inhibited and the biomechanics improved in ovariectomized rats with the treatment of G48A and alendronate given by ADFR scheme.