新型骨靶向雌激素大黄酸—雌酮抗骨质疏松活性研究

【目的】研究新型雌激素衍生物大黄酸-雌酮{新型骨靶向雌激素3-羟基-雌甾-1,3,5（10）-三烯-17酮-3-[N4-（1,8-二羟基-9,10-蒽醌-3-甲酰基）哌嗪基-N^1-乙基]醚,代号LC}对去卵巢大鼠骨密度及子宫内膜增殖的影响,探讨其抗骨质疏松活性及其对子宫的副作用。【方法】采用去卵巢大鼠模型,每天给予大黄酸-雌酮4μmol/kg（H-LC组）或0.8μmol/kg（L-LC组）,6个月后测定大鼠骨密度（BMD）、骨矿含量（BMC）及子宫重量、子宫直径、子宫内膜厚度变化,并与模型组（OVX组）,雌酚酮组（E组）比较。【结果】与OVX组相比,E组BMD及BMC增加,子宫相对重量及子宫直径均显著增加。L-LC组BMD、BMC及H-LC组BMC显著增加,达到E组水平,子宫相对重量及子宫直径虽高于OVX组,但显著低于E组。【结论】大黄酸-雌酮具有雌激素样的抗骨质疏松活性,但大大降低了对子宫的刺激性。

Effects of rhein-estrone on bone mineral density and uterus in ovariectomized rats

【Objective】To study the effects of rhein-estrone（LC）,a novel estrogen derivative,on the bone mineral density and uterus in ovariectomized rats for evaluating its activity of anti-osteoporosis and side-effect on uterus.【Methods】 The model of ovariectomized rats were used.The bone mineral density,weight and diameter of uterus the effect on uterus of model rats including,thickness of endometrium 6 months after the LC were given respectively in 4μmol.（kg·d）^-1（H-LC group） or 0.8μmol.（kg·d）^-1（L-LC group） were determined.The results were compared among the model group（OVX group）,sham-operated group（sham group） and the estrone group（E group.）【Results】In E group,the BMD,BMC,relative uterine weight,thickness of uterine endometrium and uterine diameter increased significantly as compared with OVX group.The BMD and BMC in L-LC group and BMC in H-LC group increased as compared with OVX group and showed a similar activity to E group,but the relative uterine weight,thickness of uterine endometrium and uterine diameter decreased significantly in both these two groups when compared with E group.【Conclusions】LC shows estrogen-like anti-osteoporosis activity and weaker stimulative effect on uterus than estrone.