丽江大黄二苯乙烯苷干预绝经后骨质疏松与ODF-OPG信号传导通路相关的作用机制研究

It is most urgent to find out the effective natrual-source medicines for postmenopausal osteoporosis (PMOP) which does big harm to older women. To make the kinds of non-official rhubarbs to be new drug-resoures plant, we try to excavate new medicinal potential of Rheum likiangense Sam. in our previous study. As a result, the significant effect of polyhydroxystilbenes isolated from Rheum likiangense Sam.to promote the proliferation of osteoblasts and improve PMOP of mouse have been found out via our previous investigation. This activity is equal to the synthetic estrogen and these compounds are non-toxic to experimental animals. Therefore, polyhydroxystilbenes are very promising to become a safe and efficient lead compound in the prevention of PMOP. Nevertheless, the intervention mechanism of polyhydroxystilbenes on PMOP is still not clear. Hence, our project intends to examine the related indicators of PMOP, such as BMD, BMC, E2, PICP, ICTP, in order to further clarify the effective dose of polyhydroxystilbenes on ovariectomized rats PMOP caused by the decline of endogenous estrogen levels. After that, from the view of regulation of the expression of ODF-OPG signaling pathway based on the OPG / RANKL / RANK system, we plane to explore its molecular action mechanism of polyhydroxystilbenes on PMOP through observing the mRNA expression levels of two target factors, ODF and OPG, in the bone marrow stromal cells after intervention. In a conclusion, our study will provide new perspectives as well as scientific evidence for research and development anti-PMOP natural medicines, meanwhile open up a new road to more effectively utilize abundant rhubarb resources in our country.

危害中老年妇女的绝经后骨质疏松症急需找到天然有效的药物！申请人以崭新思路尝试将药典未收载大黄变废为宝拓展为新药源植物，通过对不具备传统药效的丽江大黄进行新药用潜质的挖掘，发现其二苯乙烯苷可显著促进成骨细胞增殖、改善小鼠PMOP，其活性与合成雌激素相当，且对实验动物无毒性，有望成为安全高效的防治PMOP先导化合物。但是有关这条新发现的作用机制尚不明确！本项目拟考察BMD、BMC、E2、PICP、ICTP等与PMOP相关指标以进一步明确二苯乙烯苷对由内源性雌激素水平下降引起的去卵巢大鼠PMOP的作用效果和有效剂量；并从调控基于OPG/RANKL/RANK系统ODF-OPG信号通路表达角度，通过考察干预后骨髓基质细胞中ODF、OPG两个靶因子mRNA表达水平，探讨其对PMOP作用的深层机理和分子机制，从而为抗PMOP天然药物研发提供科学依据，为更加充分有效利用我国丰富的大黄品种和资源开辟新途径。

本项目通过对不具备传统药效的丽江大黄进行新药用潜质的挖掘，以期从崭新思路尝试将药典未收载大黄变废为宝拓展为新药源植物。研究结果发现，从丽江大黄中提取分离纯化获得的二苯乙烯苷类可显著促进成骨细胞增殖、改善小鼠PMOP，其活性与合成雌激素相当，且对实验动物无毒性，有望成为安全高效的防治PMOP先导化合物。而且，本项目考察了BMD、BMC、E2等多个与PMOP相关的指标，进一步明确了二苯乙烯苷对由内源性雌激素水平下降引起的去卵巢大鼠PMOP的作用效果和有效剂量；并从调控基于OPG/RANKL/RANK系统ODF-OPG信号通路表达角度，考察了干预前后骨髓基质细胞中ODF、OPG两个靶因子mRNA表达水平，探讨了受试物对PMOP作用的深层机理和分子机制，从而为抗PMOP天然药物研发提供科学依据，为更加充分有效利用我国丰富的大黄品种和资源开辟新途径。