蛇床子素/壳聚糖衍生物“相须”为伍抗骨质疏松的靶向效应及机制研究

基于"药食同源"、"相须"理论与"骨靶向"理念，针对蛇床子素（OST）难以吸收、水溶性差等缺陷，拟以对骨组织有强亲和力的壳聚糖衍生物（NSC）为载体，合成新型NSC-OST生物胶束，采用体外羟基磷灰石吸附及体内分布实验（RP-HPLC）验证NSC-OST的骨靶向性。在前期初步明确NSC-OST促成骨细胞分化及成骨效应的基础上，进一步优化NSC-OST的制备工艺，体内、体外系统分析NSC-OST对骨密度、骨微结构、骨代谢因子等骨质疏松药效指标的改善作用，并观察去卵巢大鼠性腺相关器官（子宫、阴道、乳腺）组织形态的变化，探讨NSC-OST的安全性，重点分析优化后的NSC-OST对介导骨形成相关的经典信号通路Wnt/β-catenin-BMP及成骨细胞内质网应激反应调控网络的影响，多角度研究其促成骨分化及骨形成的可能分子机制，揭示中医"相须"理论的内涵，为研发新型抗骨质疏松靶向药物提供实验基础。

Based on the theory of "homology of herbs and food", "mutual promotion" and "bone-targeted", the project plans to synthesize a new hydrophilic compound named NSC-OST, with water soluble chitosan derivatives(NSC), and apply hydroxyapatite adsorption experiment in vitro and distribution experiment in vivo (with RP-HPLC) to verify the NSC-OST bone targeting property, aiming at solving the major drawbacks of osthole (tough absorption and weak water solubility). The early study in vitro had clearly certificated the NSC-OST's promotion on osteoblast differentiation and osteogenesis effect. We will optimize the preparation scheme and analyze the anti-osteoporosis effect of NSC-OST depending on the change of bone mineral density, bone microstructure, bone metabolic factors and so on, and observe histomorphology changes of gonad relevant organs (uterus, vagina, breast) of OVX rats, and evaluate the safety of the NSC-OST. In this project, we intend to analyze the effect of the optimized NSC-OST on Wnt/β-catenin-BMP signal pathway and endoplasmic reticulum stress response in osteoblasts, which are pathways related to bone formation, and reveal the possible molecular mechanism of NSC-OST's anti-osteoporosis effect on osteoblast differentiation and bone formation. We expect to put forward a new interpretation of "mutual promotion" and provide the experimental basis for developing new anti-osteoporosis bone-targeted medicine.