中文摘要
骨重建稳态失衡是原发性骨质疏松症(POP)发生的基本病机,成骨细胞(OB)及其主导的骨形成(属“阴”)和破骨细胞(OC)及其主导的骨吸收(属“阳”)通过彼此分泌的调节因子形成复杂作用网络(阴阳之间的生克制化)维系骨重建平衡。基于前期临床与实验基础,课题采用老年性及绝经后POP模型,结合细胞水平,以Micro-CT、骨病理、骨密度及生物力学评价药物作用;酶免法测血中骨转换标志物,实时荧光定量PCR、免疫组化、WB、共聚焦显微镜等测骨中由OC、OB分泌的,对应调节OB、OC功能的因子(RANKL、M-CSF、Wnt5a、OPG;TGF-β、IGF、BMP、ATP6v0d2)的表达;应用神经网络建模,动态评价药物干预OP进程的作用,并构建调节因子作用网络,比较淫羊藿、女贞子配伍与单用调节骨重建的靶点或途径的差异。分析阴阳双补法防治POP的配伍机理,为中药防治POP的临床及新药开发提供科学依据。
英文摘要
The unbalance of bone reconstruction steady-state is the basic pathogenesis of the primary osteoporosis (POP). The maintenance of bone reconstruction balance depends on the complex relationship network, consisting of many regulatory factors secreted by osteoblasts (OB) or osteoclasts (OC). According to TCM theories, OB and bone formation dominated by OB belongs to the category of yang. In contrast, OC and bone resorption dominated by OC belongs to the category of yin. Based on the common understanding for POP in Chinese and Western medicine and the pre-work, two kinds of POP models (the senile and postmenopausal osteoporosis models) are used, combined with the cell level in this project. Focuses on bone reconstruction steady-state, detection techniques, including Micro-CT, bone tissue pathology, bone density and bone biomechanics are applied to evaluate drug efficacy. The serum levels of bone turnover markers will be tested by ELISA. Many regulatory factors Secreted by OB (including RANKL, M-CSF, Wnt5a, OPG) or OC (including TGF-β, IGF, BMPs, Atp6v0d2) will be tested by immunohistochemistry, western blot, real-time PCR. The application of neural network modeling is to evaluate the dynamic intervention effects on the development process of POP. Regulatory factors network will be constructed according to the experimental results. The project aims is to studies the differences of targets or pathways in the regulation of bone reconstruction among the single use of Herba Epimedii or Fructus Ligustri Lucidi and the compatibility of Herba Epimedii and Fructus Ligustri Lucidi, analyze the compatibility mechanism of nourishing yin-Yang method in prevention and treatment of POP, and provide a scientific basis for the development of new drugs on the prevention and treatment of POP.
