杜仲籽中抗绝经后骨质疏松的活性成分及其作用机制研究

Postmenopausal osteoporosis is a serious health problem that threatens the older women. Although most of anti-osteoporosis' drugs have good therapeutic effects, side effects are obvious. So, the natural compounds from plant and herbs have been paid more and more attention to by researchers for their good therapeutic effects and little side effects to treat osteoporosis. On the basis of our previous work, we found that the total iridoid glycosides from the seeds of Eucommia ulmoides can treat osteoporosis and have no side effects. We also found that aucubin is the main component of the total iridoid glycosides. According to the literature report, aucubin has positive effects on osteoblast-like cell proliferation and osteoclast inhibition. However, its mechanism is still unknown. We suspect that aucubin may be the active component of iridoid glycosides from the seeds of Eucommia ulmoides and it can affect osteoclasts by OPG/RANKL/RANK signal transduction system to treat postmenopausal osteoporosis. For this reason, we will investigate the effect of aucubin on ovariectomized rats model by observing the effects of serum biochemical parameters，hormone levels，bone mineral density and bone biomechanics. We will also clarify the pharmacodynamics mechanism of aucubin on osteoblasts and OPG/RANKL/RANK signal transduction system by molecular biology technique and enzyme linked immunosorbent assay method. Our research will provide new method and new target point for preventing and treating postmenopausal osteoporosis.

绝经后骨质疏松症(PMOP)己成为威胁老年女性健康的严重骨病。目前抗PMOP的药物存在较多副作用，而天然植物化合物为寻找疗效好、副作用低的新药物提供了研究方向。在前期研究中，我们发现杜仲籽总环烯醚萜苷可治疗PMOP且未见副作用，进一步分离总环烯醚萜苷得到其主成分桃叶珊瑚苷。文献报道桃叶珊瑚苷具有促进成骨细胞增殖和抑制破骨细胞增殖的作用，但其作用机制尚不清楚。我们推测桃叶珊瑚苷是杜仲籽总环烯醚萜苷抗PMOP的单体活性成分，并通过OPG/RANKL/RANK信号传导系统作用于破骨细胞来抗PMOP。为此，我们拟采用去卵巢大鼠PMOP模型，从整体水平上考察桃叶珊瑚苷抗PMOP的作用；采用分子生物学、ELISA等技术，从细胞及分子水平上考察桃叶珊瑚苷对成骨细胞增殖、分化及对OPG/RANKL/RANK信号传导系统的影响，阐明桃叶珊瑚苷抗PMOP的作用机制，为防治PMOP提供新思路和药物作用的新靶点。

绝经后骨质疏松症(PMOP)己成为威胁老年女性健康的严重骨病。目前抗PMOP的药物存在较多副作用，而天然植物化合物为寻找疗效好、副作用低的新药物提供了研究方向。在前期研究中，我们发现杜仲籽总环烯醚萜苷可治疗PMOP且未见副作用，进一步分离总环烯醚萜苷得到其主成分桃叶珊瑚苷(AU)。为此，本课题采用去卵巢大鼠PMOP模型，从整体水平上考察AU抗PMOP的作用；采用分子生物学、ELISA等技术，从细胞及分子水平上考察AU对成骨细胞增殖、分化及对OPG/RANKL/RANK信号传导系统的影响，得到以下结论：(1)AU能够通过增加骨密度和改善骨小梁微结构，包括提高了骨密度、相对骨体积、骨小梁数量、骨小梁厚度和连接密度指数，降低了骨小梁分离度和结构模型指数，来改善大鼠股骨的结构力学参数，提高骨折力和骨压碎力。并且与雌激素相比较具有无子宫刺激等副作用的优点。(2)10-7mol/L浓度AU能够显著的增加大鼠原代成骨细胞的增殖、碱性磷酸酶的活性和矿化结节形成的数量，并通过改变成骨细胞OPG、RANKL基因和蛋白的表达、上调OPG与RANKL的比值从而抑制破骨细胞的增殖和分化，这是AU对骨系统发挥良性作用、抑制PMOP发生的分子机制之一。AU可能成为防治 PMOP的新的天然药物，具有潜在的开发利用价值。