哌嗪雌酚酮对去卵巢大鼠骨代谢的作用

Piperazinyl estrone prevents bone loss in ovariectomized rats

目的 研究哌嗪雌酚酮 (一种新合成雌激素哌嗪类衍生物 )对去卵巢大鼠骨代谢及子宫的作用。方法雌酚酮 (E) 0 75mg·kg- 1 ·d- 1 ,哌嗪雌酚酮 (P E) 1和 10mg·kg- 1 ·d- 1 ,ig共 90d ,骨形态计量学测量。结果 去卵巢大鼠子宫萎缩 ,血清胆固醇升高 ,骨量减少伴骨高转化的改变。E组与去卵巢组比 ,子宫重量增加 ,血清胆固醇降低 ,骨高转化降低。P E(1mg)组与去卵巢组比 ,子宫重量轻微增加 ,骨量增加 ,骨形成和骨吸收均维持在去卵巢组的高水平。P E(10mg)组比低剂量组增加更多的骨量 ,但其作用机理与雌酚酮相同 ,明显地降低骨转化。结论 哌嗪雌酚酮可预防去卵巢大鼠所致的骨丢失。低剂量 (1mg)

Aim To determine the effect of piperazinyl estrone, a new estrogen derivative, on bone turnover, bone mass and uteri in ovariectomized rats. Methods Female Sprague Dawley rats were ovariectomized (OVX) or sham operated (sham) at the age of 3 months and treated with estrone (E) at 0 75 mg·kg -1 ·d -1 , or with piperazinyl estrone (P E) at 1 or 10 mg·kg -1 ·d -1 , orally, for 3 months. At the time of death, the uterine weight was measured. Bone histomorphometric analysis of proximal tibial metaphyses (PTM) was performed in undecalcified sections. Results Bone histomorphometric data showed that the percent trabecular area (%Tb.Ar) of OVX rats with bone high turnover was significantly decreased. The uteri were atrophied. The percent trabecular area (%Tb.Ar) of estrone treated group was increased in decreasing bone turnover manner. But the size and weight of uteri in this group were increased vs OVX group. The bone loss induced by OVX was preserved by P E treatment, but the mechanism of maintaining bone is different from that of E treated rats. P E treatment in low dose did not decrease any bone formation indices, such as percent labeling perimeter, bone formation rate per bone volume (BFR/BV), except bone mineral apposition rate (MAR) compared with E treated group, and maintained them at OVX level. The uteri were found to be in atrophy compared with the match dose (0 75 mg) of E treated OVX rats. But rats treated with high dose of P E showed the same change like E treated group. Conclusion The finding of this study shows that lower dosage of piperazinyl estrone has effect on preventing the bone losses in OVX rats, while the bone formation and the uterus are not affected, thus supporting the hypothesis that piperazinyl estrone has the potential to prevent postmenopausal bone loss in women with less side effects.