杜仲丸对胎动、骨痿“异病同治”的药效物质群-症-症关联性规律研究

Duzhong Wan, from "Zhengzhi Zhunsheng", is possessed for tonifying kidney and preventing effects of miscarriage. Our group have previously found Duzhong Wan had the activity of anti-osteoporosis, which belongs to "bone atrophy" category. Duzhong Wan could treat threatened abortion and osteoporosis of the kidney deficiency through treating different diseases with the same therapy. However, the connectivity of diseases and effective ingredient groups of Duzhong Wan is still unclear. Therefore, we think that the effective ingredient groups of Duzhong Wan for threatened abortion and osteoporosis are different. Moreover, different effective substance groups could regulate indicators of "fetal disorder" and "bone atrophy disease". And the same group of effective substances or the different ones could regulate the kidney deficiency which is related to sex hormones. By establishing the efficacy of osteogenic database according to the serum samples for the kidney deficiency, kidney-related hormone, miscarriage and other indicators in the above two animal models, characterizing the various of substance groups in drug-containing serum using LC-Q/TOF-MS and LC-QQQ/MS, identifying effective substance groups, validating the activities of effective substance groups, measureing expression levels of target proteins and evaluating the effect on the binding of ligands to receptors, and analyzing the groups of substances database and efficacy database using partial least squares analysis, we will try our best to reveal the inter-connectivity between diseases and characteristics of effective substance groups and rules of Duzhong Wan for treating different diseases with the same therapy based on the type of effective substance groups, the proportion of active contribution and related differences. Furthermore, this study could also be benefit for exploring a critical scientific issue on how the classical prescription of Duzhong Wan responds well to treatment in different diseases of threatened abortion and osteoporosis with the same therapy.

杜仲丸源于《证治准绳》，功效“补肾、安胎”。申请者研究发现杜仲丸具有治疗骨质疏松活性，骨质疏松症属于中医“骨痿”范畴。杜仲丸治疗胎动症和骨痿症为肾虚证的“异病同治”，其“异病同治”的药效物质群-症-症关联性规律尚不清楚。我们认为：杜仲丸在“肾虚胎动模型”和“肾虚骨痿模型”大鼠血清中药效物质群存在差异，相同的药效物质群调控了与“肾虚”相关的性激素指标，不同的药效物质群调控了两症各自的指标，在不同的病理状态下也调控了两症的共有指标。以各模型含药血清的化学成分群表征为切入点，性激素水平及其胎动因子、骨痿因子变化为评价指标，两种肾虚大鼠模型对各药效物质群活性验证为手段，组织/细胞中靶蛋白受体表征和受体-配体结合变化对各药效物质群活为佐证，偏最小二乘法为分析工具，揭示杜仲丸“异病同治”药效物质群-症-症关联性特征，探索经方杜仲丸对胎动和骨痿“异病如何同治”的关键科学问题。