减味寿胎丸补肾安胎组分配伍及其药效机制研究

Based on the clinical advantages of Chinese Medicine in reproductive health field, considering Shou Tai Wan (STW), which is the representative recipe of invigorating the kidney and miscarriage prevention as research target, using cell model and animal model which aim at the main pathological element of spontaneous abortion (SA) to analyze the effects of the compatibility of different components of the recipe for the main target and its possible mechanisms with pharmacological and Molecular target technologies, and study the synergism action rule of the compatibility of different components. 1) Applying homogeneous design method to research the kidney invigorating and miscarriage prevention effect of the recipe and different dosage compatibility of different components of the recipe, and using cell model to screen the best dosage combination of the effective components. 2)Based on ① For endocrine factors, using the abortion animal models of corepus luteum inhibition due to renal deficiency rats and in vitro cytotrophoblast cells as research carriers, systematical investigate the Pharmacodynamic material basis of invigorating the kidney and miscarriage prevention effect, the Signal transduction pathway and the action rule of the compatibility of different components of the recipe. And use the fluorescent tracer method to tract the drug components and the interaction of the target protein under normal physiological and pathological conditions as well. ②Aiming at the Immunomodulator of the maternal-fetal interface, applying Targets agonist and antagonist to study the CBA / J × DBA / 2 mouse abortion model and the targeted gene knockout animal models so as to explore the immunologic balance regulation role and mechanisms of the compatibility of different components. 3) Utilizing HPLC-MS technology to detect the contents and pharmacokinetic parameters of the recipe and the main effective ingredients of the new compatible recipe.

根据生殖健康领域中医药的临床优势，以补肾安胎基础方减味寿胎丸为研究对象，针对发生SA的重要病理环节，利用细胞模型和病证结合模型，整合中药分析、药理、分子靶标技术手段，分析不同组分及配伍对主要靶点的作用及机制，研究组分配伍协同增效的作用规律：1）均匀设计法研究复方及各单味药有效组分的不同剂量组合的补肾安胎药效，用细胞模型筛选出最佳药效配伍的有效成分组合。2）基于上①针对内分泌，以肾虚-黄体抑制流产大鼠模型和离体滋养叶细胞为载体，系统研究补肾安胎药效物质基础、信号传导途径和组分配伍作用规律，并通过荧光示踪法跟踪药物组分-靶蛋白在正常生理和病理环境下的相互作用；②针对母胎界面免疫调节，应用作用靶点激动剂、拮抗剂研究CBA/J×DBA/2小鼠流产模型和靶点基因敲除动物模型，探讨不同组分配伍调节免疫平衡的作用及机制。3）应用HPLC-MS检测复方及新配伍组方中主要有效成分的含量及药代动力学参数。

按照原计划完成研究任务。以补肾安胎基础方减味寿胎丸为研究对象，构建滋养细胞和蜕膜细胞损伤模型和病证结合模型，均匀设计法研究复方及各单味药有效组分的不同剂量组合的补肾安胎药效，用细胞模型筛选出最佳药效配伍的有效成分组合，申请国际专利1项。以蜕膜细胞和离体滋养细胞为载体，系统研究补肾安胎药效作用机制。完成针对母胎界面免疫调节，研究补肾安胎方对CBA/J×DBA/2 小鼠流产模型调节免疫平衡的作用及机制。完成应用UPLC-MS 检测复方及新配伍组方中主要有效成分的含量及药代动力学参数，申请国内专利2项。