xy2004对去势雌鼠骨质疏松的保护作用及机制  

Protective effect of xy2004 on postmenopausal osteoporosis in ovariectomized rats and the mechanism

作　　者：侯进[1] 李萍[1] 曾菊绒[1] 胥晓丽[1] 魏明[1] 熊晓云 弥曼[1] 

机构地区：[1]西安医学院基础医学部药理学与毒理学教研室,西安710021 [2]西安利君制药有限责任公司,西安710077

出　　处：《中国骨质疏松杂志》2014年第5期500-503,共4页Chinese Journal of Osteoporosis

基　　金：国家自然科学基金(F050903);陕西省教育厅专项科研项目(2010JK805);西安医学院博士科研启动基金(2011DOC04);西安医学院扶植基金(2009FZ2)

摘　　要：目的研究苯并二氢吡喃衍生物xy2004对去势雌鼠骨质疏松的治疗作用,并初步探讨其机制。方法将50只SD大鼠随机分为5组,假手术组、模型组、genistein组、xy2004高、低剂量组。假手术组、模型组均给予蒸馏水10 mL·kg-1,给药组分别给予小剂量xy2004 3 mg·kg-1和大剂量xy2004 7 mg·kg-1,genistein组给genistein 6 mg·kg-1,灌胃给药。观察xy2004对去势雌鼠骨密度的影响;检测大鼠体内血清钙、血清磷及碱性磷酸酶、白细胞介素-6等生化指标;用放射性配体结合法考察化合物与雌激素受体(estrogenic receptor,ER)的亲和力。结果去势后大鼠骨密度下降,使用xy2004灌胃3个月后,能明显抑制去势雌鼠骨密度的下降,降低血中ALP含量,抑制IL-6分泌。Xy2004与ER有亲和力,对ERα和ERβ的IC50分别为4.12×10-7M和7.38×10-5M。结论化合物xy2004通过与去势雌鼠体内雌激素受体结合,影响去势大鼠骨代谢,增强去势雌鼠骨密度,抗去势雌鼠骨质疏松。Objective To investigate the therapeutic effect of xy2004, a kind of benzene and dihydropyran derivatives, on postmenopausal osteoporosis in ovariectomized rats, and to preliminarily explore its mechanism.Methods Fifty female SD rats were divided into 5 groups：sham operation group, ovariectomized group （ OVX） , genistein group, xy2004 high dose group, and xy2004 low dose group.Forty SD rats were ovariectomized except 10 rats in sham operated group.Rats in sham operated group and OVX group were treated with 10 ml/kg distilled water.Rats in xy2004 high and low dose group were treated with 7 mg/kg and 3 mg/kg xy2004, respectively.And rats in genistein group were treated with 6 mg/kg genistein.All the drugs or distilled water were given through gavage administration.The effect of xy2004 on bone mineral density （ BMD） in OVX rats was observed.The serum levels of calcium, phosphorous, and IL-6 were detected.The affinity of xy2004 to estrogenic receptor （ ER） was detected using radio-ligand binding assay.Results BMD in OVX rats decreased.After 3-month gavage, xy2004 could significantly inhibit the decrease of BMD in OVX female rats, reduce serum ALP level, and inhibit the secretion of IL-6.The affinity of xy2004 to ER was detected, and the IC50 to ERαand ERβwas of 4.12 ×10 -7 M and 7.38 ×10 -5 M, respectively.Conclusion By binding with ER in female OVX rats, xy2004 can affect bone metabolism in rats , improve BMD in female OVX rats, and prevent postmenopausal osteoporosis in OVX rats .

关 键 词：骨质疏松 雌激素受体(ER) ESTROGEN receptor (ER) 

分 类 号：R68[医药卫生—骨科学]