目的 探讨淫羊藿素（IT）与核因子-κB受体活化因子配体（RANKL）蛋白靶点结合能力，并阐明其抗骨质疏松作用机制。方法 采用分子对接技术模拟并预测RANKL与IT的相互作用，并通过切除大鼠双侧卵巢制备骨质疏松模型，评价IT对模型大鼠体质量、骨吸收血清指标碱性磷酸酶（ALP）和抗酒石酸盐酸性磷酸酶-5b（TRACP-5b）、骨密度（BMD）以及骨组织形态的调节作用。结果 IT可与靶蛋白RANKL发生稳定对接，IT组大鼠体质量较模型组显著降低（P<0.05），IT能显著降低模型大鼠血清ALP、TRACP-5b水平（P<0.01），显著降低模型大鼠股骨表面积与体积比值（BS/BV）、骨小梁分离度（Tb.Sp）值（P<0.01），显著增加BMD、骨体积分数（BV/TV）、骨小梁厚度（Tb.ThN）、骨小梁数目（Tb.N）值（P<0.01）。结论 IT能通过与RANKL蛋白靶点结合，抑制破骨细胞分化并发挥抗骨质疏松作用。

Objective To demonstrate that icaritin (IT) inhibits bone resorption against osteoporosis by binding to RANKL protein targets. Methods The effects of RANKL and IT on the osteoporosis of ovariectomized rats were established by molecular docking technique. The effects of IT on the body weight, bone resorption serum index (ALP and TRACP-5b), bone mineral density and bone morphology of OVX rats were evaluated. Results IT could be stably docked with target protein RANKL. The body weight of IT group was significantly lower than that of OVX group (P < 0.05). IT could significantly decrease the levels of serum ALP and TRACP-5b (P < 0.01), and the value of femur BS/BV and Tb.Sp (P < 0.01) in OVX rats. Moreover, IT significantly increased BMD, BV/TV, Tb.ThN, Tb.N values (P < 0.01). Conclusion IT can inhibit osteoclast differentiation and play anti-osteoporosis by binding with RANKL protein target.

南京市药学会常州四药科研项目（2016YX007）；扬州市自然科学基金面上项目（YZ2016131）；国家自然科学基金资助项目（81703773）；江苏省自然科学基金资助项目（BK20170560）；江苏省博士后基金资助（1601184C）