香豆雌酚对去卵巢大鼠骨代谢生化指标的影响

Effects of coumestrol on biochemical markers of bone metabolism in ovariectomized rats

目的研究香豆雌酚对去卵巢大鼠骨代谢生化指标的影响,探讨香豆雌酚对绝经后骨质疏松的防治作用。方法 36只6月龄雌性SD大鼠,随机分为去卵巢模型组,香豆雌酚组,17β-雌二醇组和假手术组,手术后14d,各组开始进行干预治疗。17β-雌二醇组按300μg/kg皮下注射,每周两次;香豆雌酚组按60 mg/kg皮下注射,1次/d;去卵巢模型组与假手术组每日皮下注射与17β-雌二醇组和香豆雌酚组同等体积的生理盐水。在干预治疗开始的第1～10周,每周测1次大鼠质量。第11周时测定尿钙、尿磷、尿肌酐和尿脱氧吡啶啉;计算大鼠子宫系数;测血钙、血磷、血碱性磷酸酶、血雌二醇浓度;测量大鼠右侧股骨密度。结果与去卵巢模型组相比,香豆雌酚组大鼠骨密度(g/cm2)明显升高(0.141±0.002和0.126±0.003,P<0.05),血碱性磷酸酶(1.26±0.15和2.42±0.70)、尿钙/尿肌酐(0.207±0.059和0.217±0.047)、尿脱氧吡啶啉/尿肌酐(6.056±1.715和0.572±3.140)(P均<0.05)下降,差异有显著性意义,血雌二醇(7.13±4.11和3.41±1.98)升高;与17β-雌二醇组相比,香豆雌酚组子宫系数(g/kg)明显降低(1.056±0.715和4.133±1.121,P<0.01),差异有显著性意义。结论香豆雌酚具有减少骨吸收,促进骨形成,增加骨密度的作用,而其对子宫组织的副作用弱于雌激素。

Objective To study the effects of coumestrol on biochemical markers of bone metabolism in ovariectomized rats and to explore the therapeutic effect of coumestrol on postmenopausal osteoporosis. Methods Thirty-six 6-month old female SD rats were randomly divided into ovariectomized model group, coumestrol group, 17β-estradiol group, and the sham group. The intervention therapy started 14 days after the operation in each group. Rats of 17β-estradiol group were treated with 300 μg/kg 17β-estradiol subcutaneously, twice a week. Rats of coumestrol group were treated with 60 mg/kg coumestrol subcutaneously, once a day. Rats of ovariectomized group and the sham group were injected daily with normal saline of the same volume as those in the 17β-estradiol and coumestrol groups. Body weight of the rats was measured in the first 10-week. On 11 weeks, urinary calcium, phosphate, creatinine, and deoxypyridinoline were measured. Rat uterus coefficient was calculated. Serum calcium, phosphorus, alkaline phosphatase, estradiol levels, and bone mineral density were also determined. Results Bone mineral density （ g/cm2 ） in rats of coumestrol group was significantly higher than that in OVX model （0. 141±0.002 vs0.126 ±0.003, P〈0.05）. Serum alkaline phosphatase （1.26± 0.15 vs 2.42 ±0.70）, urine calcium/urine creatinine （0. 207 ± 0. 059 vs 0. 217 ± 0. 047 ） , urinary deoxypyridinoline/urine creatinine（6.056 ±1. 715 vs 0. 572 ± 3. 140） in rats of eoumestrol group decreased compared to those in OVX model （ P 〈 0.05 ） , and the differences were statistically significant. Serum estradiol in rats of coumestrol group was significantly higher than that in OVX model （7.13 ±4.11 vs 3.41 ± 1.98 ）. The uterine factor （g/kg） in rats of eoumestrol group was significantly lower than that in 17β-estradiol group （ 1. 056±0. 715 vs 4. 133 ± 1. 121, P 〈0. 01 ）, and the difference was statistically significant. Conclusion Coumestrol can effectively reduce the bone absorption, promote the bone formation, and increase bone mineral density. The side effect of coumestrol on uterine tissue was lower than that of estrogen.