淫羊藿素逆转糖皮质激素所致骨质疏松及其与Runx-2靶点的相互作用研究

Icaritin reversed glucocorticoid induced osteoporosis and its interaction with Runx-2 targets

目的阐明淫羊藿素(icaritin,IT)对糖皮质激素所致骨质疏松的治疗作用,解析Runt相关转录因子2(runt-related transcription factor 2,RUNX-2)与IT的作用机制。方法采用泼尼松龙(prednisolone,PNSL)抑制斑马鱼骨形成,头骨染色后,评价IT对斑马鱼头骨染色面积、累计光密度和矿物元素含量;通过结合分子对接(molecular docking)技术分析RUNX-2与IT的分子间作用。结果PNSL显著抑制了斑马鱼矿化骨面积、累积光密度和Ca、P含量(P<0.01);经IT干预后,斑马鱼的上述指标均有显著性升高(P<0.01);计算机拟合数据显示,IT可与RUNX-2能稳定对接,其分子对接得分为-5.46986055,结合位点主要是3号位的-OH和2号位的苯环。结论IT能与RUNX-2受体结合,促进斑马鱼的骨形成。

Objective To elucidate the therapeutic effect of icaritin(IT)on glucocorticoid induced osteoporosis,and to analyze the mechanism between runt related transcription factor 2(Runx-2)and IT.Methods Prednisolone(PNSL)was used to inhibit the skull formation of zebrafish.After skull staining,the effects of IT on the area of staining,the accumulated optical density and the content of bone mineral elements in zebrafish skull were evaluated.The molecular interaction between Runx-2 and IT was analyzed by molecular docking technology.Results PNSL significantly inhibited the mineralized bone area,accumulated optical density and Ca,P content of zebrafish(P<0.01);Under the intervention of IT,the above indicators were significantly increased(P<0.01);Computer fitting data showed that IT and Runx-2 could stably docking,and the scores of molecular docking was-5.46986055,the binding sites were mainly-OH at position 3 and benzene at position 2.Conclusion IT can bind to Runx-2 receptor and promote bone formation in zebrafish.