基于动脉粥样硬化家兔模型研究痹病药膳方代谢组学与配方优化

Metabonomics and formula optimization of Bibing Yaoshan prescription based on atherosclerosis rabbit model

目的研究痹病药膳方的配伍规律和作用机制,为其深入研发提供科学依据。方法使用动脉粥样硬化(AS)家兔模型,研究血脂水平、血液流变学和主动脉弓形态评价优化方剂配方;使用LC-MS技术比较研究各配方血清代谢组学,最优配方血清、心和肝代谢组学阐述其代谢机制。结果痹病药膳方最优配方为鸡血藤、土茯苓和黄芪(配方3);血清中3种配方共有药效代谢差异物24个,配方3特有药效代谢差异物8个,配方1与配方2药效代谢差异物差异较小,配方3与其它两个配方药效代谢差异物差异较大;配方3在血清、心和肝中药效代谢差异物较大,在肝中鉴定的药效代谢差异物最多、心其次,配方3在血清、心和肝中共有的药效代谢差异物较少;配方1和配方2的代谢机制差异很小,配方3与其它两个配方差异较大;配方3在不同组织器官中的药效差异比较大。结论配方3为最佳配方,血清中配方3与其它两个配方代谢轮廓差异比较大;配方3在不同组织和器官中代谢轮廓差异较大。

Objective To study the compatibility regularities and mechanisms of action of the Bibing Yaoshan prescription,providing a scientific basis for its further research and development.Methods Using an atherosclerosis(AS)rabbit model,this research evaluated optimal formulations by examining blood lipid levels,hemorheology and aortic arch morphology.LC-MS technology was employed to conduct comparative serum metabonomic studies of various formulations and elucidate their metabolic mechanisms,specifically focusing on the most optimal formula in serum,heart and liver.Results The optimal Bibing Yaoshan prescription formulation included Suberect spatholobus,Smilax glabra Roxb,and Astragalus membranaceus(Formula 3).there were 24 pharmacodynamic metabolites in serum among the three formulas,with eight specific to Formula 3,the difference of pharmacodynamic metabolites between Formula 1 and 2 was not obvious but between Formula 3 and other two formulas was significant.Notable variations in pharmacodynamic metabolites of Formula 3 were seen in serum,heart and liver,with the highest identification of pharmacodynamic metabolites in the liver,followed by the heart,Formula 3 has fewer mutual pharmacodynamic metabolism differences in serum,heart and liver.The metabolic mechanism differences between Formulas 1 and 2 were minor,while Formula 3 differed notably from the other two formulas.Formula 3 exhibited substantial variation in effect across different tissues and organs.Conclusion Formula 3 emerged as the most optimal,displaying significantly distinct metabolic profiles in serum compared to the other two formulas.the metabolic profile of Formula 3 varies greatly in different tissues and organs.