基于SBD-Zebrafish-CMOEA三联法对紫穗槐保肝降酶活性组分的定量组效关系研究

It is one of urgent and key scientific problems on the process of researching modern chinese medicine that how to elucidate the therapeutic material basis (TMB) of Traditional Chinese Medicine (TCM) efficiently. Previous studies have suggested that Quantitative Composition–Activity Relationship (QCAR) study is an effective method, although it has problems such as complicacy in modeling, difficulty in optimization of pharmacodynamics multi-index and low-efficiency of activity assessment by traditional animal model. This study advances an new QCAR model based on SBD (Simplex Barycenter Design)-Zebrafish-CMOEA (Mult-objective Evolutionary Algorithm based on Cloud Model) to solve the problems mentioned above. Components of Amorpha fruticosa are selected as study object, SBD is used to construct calculation model, pharmacodynamics is evaluated by acute liver injury model induced by CCl4 and D-galactosamine, and pharmacodynamics multi-indices are optimized by CMOEA, all these are aimed to discuss the effects of the components on the key index of serum ALT and AST. And finally a new research model which is suitable to prescription with ingredients less than 5 and singles is provided to reveal the TMB of TCM. Such a model with simple calculation model, high-efficiency of activity assessment, fast and accurate muti-objective optimization, may be significant to the modern TCM research and quality control of Chinese medicinal materials.

如何高效地阐明中药药效物质基础是现代中药创制过程中急需解决的关键科学问题之一。既往的研究表明，定量组效关系（QCAR）研究是一种行之有效的方法，但存在着建模复杂、基于传统动物模型的活性评价低效、多药效指标优化困难等问题。本课题提出一种基于单形重心设计（SBD）-斑马鱼（Zebrafish）-云模型多目标进化算法（CMOEA）三联法的QCAR研究新模式，以利于上述问题的解决。我们选用紫穗槐保肝降酶活性组分为研究对象，以SBD建立计算模型，以四氯化碳和D-氨基半乳糖诱导的斑马鱼急性肝损伤模型进行药效评价，以CMOEA进行多药效指标寻优，探讨各组分对关键药效指标血清ALT和AST的影响，从而为中药药效物质基础研究提供一种新的研究模式。该模式建模简单、药效评价高效、多目标优化快速准确，特别适用于五味以下的小处方及单味中药的药效物质基础研究，对现代中药的研发和中药材质量控制均具有重要意义。

如何高效地阐明中药药效物质基础是现代中药创制过程中急需解决的关键科学问题之一。既往的研究表明，定量组效关系（QCAR）研究是一种行之有效的方法，但存在着建模复杂、基于传统动物模型的活性评价低效、多药效指标优化困难等问题。本课题提出一种基于单形重心设计（SBD）-斑马鱼（Zebrafish）-云模型多目标进化算法（CMOEA）三联法的QCAR研究新模式，以利于上述问题的解决。我们选用紫穗槐保肝降酶活性组分为研究对象，以SBD建立计算模型，以硫代乙酰胺（TAA）诱导的斑马鱼急性肝损伤模型进行药效评价，以CMOEA进行多药效指标寻优，探讨了各组分对关键药效指标血清ALT和AST的影响，从而为中药药效物质基础研究提供一种新的研究模式。该模式建模简单、药效评价高效、多目标优化快速准确，特别适用于五味以下的小处方及单味中药的药效物质基础研究，对现代中药的研发和中药材质量控制均具有重要意义。