基于同种异位不同药性姜黄、郁金的“量－性”规律研究

The research is based on 973 plans "Chinese medicine property theory inherited and innovation research".The research object is rhizoma curcumae longae and radix curcumae which are clinical common Chinese medicines and from different part of the same plant and have the same acrid and bitterness taste ,but have different chinese medicine property that rhizoma curcumae longae is warm property and radix curcumae is cold property. The research advances the science hypothesis that think the Chinese medicine property has material base (effective components) and the relationship between the Chinese medicine property and effective components is not only reflected in the different kinds of effective components and also reflected in the content of effective components and exists the law of quantity and property of Chinese herbal medicine. We will use HPLC-MS fingerprint technology and compare the fingerprint of the secondary metabolism products, extraction and the animal serum to expound the material base of the rhizoma curcumae longae and radix curcumae.We will compare the components absorption between in cold syndrome State, heat syndrome State and normal State to expound the effective components group which represent the Chinese medicine property of rhizoma curcumae longae and radix curcumae. We will use the animal mode related of disease and syndrome and research the relationship between the content changes of effective components group and efficacy to clear the volume effect relationship.We have the theory for guide that think the property for body and effect for use to Chinese medicine and there is the automatic link between the effective components, effectiveness and the chinese medicine property.The research is to reveale the modern scientific connotation of traditional chinese medicine about the law between the amount of active ingredient and chinese medicine property and the beneficial exploration of the theory of traditional Chinese medicine property.

本课题基于973计划"中药药性理论继承与创新研究"研究基础，以同种异位的姜黄和郁金为研究对象，两者为临床常用中药，均具辛苦味，但姜黄性温，郁金性寒，围绕"中药药性是有物质基础（有效成分）的，中药药性与有效成分之间不仅体现在有效成分不同即质的变化，还体现在含量的变化上，即存在"量性"规律"的科学假说，采用HPLC-MS指纹图谱技术，通过姜黄和郁金的次生代谢产物、提取物及含药血清图谱间比较，阐明两者体内作用的物质基础，比较两者在寒证、热证状态下与正常状态下的药物成分吸收情况，阐明姜黄性温、郁金性寒的有效成分群；采用与疗效相关的病证结合动物模型，研究有效成分群含量变化与药效之间的关系，明确其量效关系，以中药以"性"为体，以"效"为用的理论为指导，根据"有效成分－功效－药性"三者之间存在着必然的联系，探讨有效成分的量与药性之间的规律，揭示中药药性"量性"规律现代科学内涵，是中药药性理论的有益探索。

中药药性理论是中医药的核心理论之一，是指导中医药临床用药的基本原则，本项目选取姜黄、郁金为研究对象，二者来源于同一植物的不同药用部位，但寒、热药性却相反。.本项目主要研究内容为基于液质的姜黄、郁金体内作用物质基础研究、基于代谢组学的姜黄、郁金寒热药性差异研究以及有效成分含量与药性之间的“量-性”规律分析。.研究结果如下：.1、基于液质的成分分析研究表明，从鉴定出的生物标志物可以看到，姜黄素类化合物和萜类化合物在姜黄和郁金中均有显著差异，姜黄中姜黄素、去甲氧基姜黄素、双去甲氧基姜黄素、Dihydrocurcumin、Ar-turmerone，α,β-turmerone（bisacumol）， Zingiberene（β-bisabolene，β-curcumene）在姜黄中的含量均高于郁金，且具有显著性差异。.2、基于代谢组学和药效研究表明，姜黄、郁金对热证模型内源性代谢产物均有一定调节作用，但郁金调节作用更为明显。与热证模型组比较，郁金给药组中的苏氨酸、甘氨酸、苯丙氨酸均显著下调，柠檬酸、半乳糖、甘露糖、甘油、油酸、亚油酸也明显降低，说明郁金对热证模型所导致的黄疸、肝损伤、能量代谢、脂肪代谢均具有一调节定用，而姜黄主要对模型组中氨基酸具有一定调节作用。药效研究表明，郁金水煎液对血清ALP、TG具有明显降低作用，提示郁金对脂肪代谢具有调节作用，与代谢组学研究一致。.姜黄、郁金对寒证模型内源性代谢产物均有一定调节作用，姜黄调节作用更为明显。姜黄对寒证模型干预后，与模型组区分明显，苏氨酸、丙氨酸、苯丙氨酸等生物标志物均有较明显下降，柠檬酸、苹果酸、半乳糖、甘露糖等糖代谢产物也显著回升，说明机体的代谢水平向正常方向回归；郁金给药组对寒证模型的调节作用则小于姜黄，油酸、胆固醇等脂肪代谢产物明显降低。.3、综合成分分析、药效结果和代谢组学分析，有效成分（群）是药物发挥疗效的物质基础，药理效应是药性的体现，性效一致；药性与有效成分（群）含量在一定范围内存在“量性”规律。姜黄素类化合物和萜类化合物是姜黄和郁金发挥疗效的物质基础，且含量差异显著。针对寒证模型组，姜黄对寒证模型代谢谱的调节作用大于郁金，这一点印证了“姜黄性温”的理论；针对热证模型组，郁金对热证模型代谢的影响大于姜黄，从一个侧面反映出郁金具有“寒性”的性质。