基于中医方证代谢组学的开心散干预老年痴呆症大鼠的效应物质动态分析

目的：本研究在开心散干预氯化铝联合D-半乳糖诱导老年痴呆症大鼠模型有效性的基础上，揭示开心散对老年痴呆症（AD）不同阶段干预作用的代谢物靶点，构建开心散体内成分与内源性生物标记物的网络关系，分析开心散对AD发展过程干预作用的效应物质的动态变化。方法：利用行为学指标评价模型复制进程以及开心散的干预作用；运用代谢组学技术和方法分析开心散对AD大鼠模型不同阶段干预作用的靶点；应用UPLC-MS技术和MSE质谱数据采集模式，分别对开心散体外化学成分和口服给药后的血中移行成分进行表征及鉴定；利用PCMS手段，构建复方药效物质基础与内源性生物标记物的数理模型，发掘开心散防治老年痴呆症不同阶段的效应物质。结果：给予AD大鼠开心散溶液治疗后，模型大鼠的认知功能得到改善，其病理学进程得以延缓。代谢组学研究表明，开心散对AD模型不同阶段标记物的异常表达起到恢复作用，体现了开心散干预老年痴呆症多靶点、多途径的特点。结论：基于中医方证代谢组学方法为开心散减缓AD进程研究提供了新的思路。

Dynamic Analysis of the Effects of Pharmacodynamic Constituents of Kai Xin San on Alzheimer's Disease Rats Based on Chinmedomics

The present study aimed at elucidating the therapeutic effects of Kai Xin San(KXS)on AD rat models induced by D-gal and AlCl₃,and investigating its metabolic products of KXS and their functions using metabolomic technique by establishing the network relations between chemicals of KXS and endogenous biomarkers selected by metabolomics with the analyze of the dynamic changes of pharmacodynamic basis of KXS preventing AD.The typical behavior tests were adopted to evaluate the state of AD in model rats and the therapeutic effects of KXS.Metabolomic technologies were used to reveal the potential biomarkers of AD and the target spots after the administration of KXS.Serum pharmacochemistry of TCM was herein introduced to explore the constituents absorbed into the blood after lavage administration of KXS.The constituents,targets of the influenced metabolic pathways,can be determined as the pharmacodynamic basis at different pathogenic stages of AD.The effect of pharmacodynamic basis was verified,while multi-component and multi-target synergistic mechanism behind prevential and therapeutic effects of KXS in AD rats was elucidated in this study.AD rat models induced by AlCl₃ and D-gal received the intragastric administrated of KXS.As a result,the Morris water maze test showed that AlCl_{3,/sub> and D-gal-induced learning disability and memory loss of the AD rats were mitigated within the administration of KXS.The metabonomics studies showed that the abnormal expressions of biomarkers of the rats at different stages of AD were regulated and restored featuring the multi-target and multi-path of the administration of KXS.In conclusion,Chinmedomics is an novel discipline for addressing the problem in the effects of Chinese materia medica and other related scientific issues.}