基于药性表征-药效-物质基础关联的姜黄连炮制机理研究

Medicines' nature is the basic characteristics of Chinese Medicines. It's better to understand the purpose and effects of processing based on the study on the relationship between the changes of nature, pharmaceutical effects and material base. Processing Rhizoma Coptidis(RC, cold and bitter nature) with jinger juice(hot nature)is consistent with the processing theory in Taditional Chinese Medicine. According to the main purposes of "moderating cold nature, strengthening the effects of regulating the stomach and stopping vomit" of jinger juice-processed RC, the ethology experiment, morphological observation in rats, energy index determination and metabolism will be applied to evaluate the effects of 'moderating cold nature', the effects of antimicrobial activity, stopping vomit, regulating stomach and protective effects of gastric mucosa damage of raw and jinger juice-processed RC will be observed to determine another processing purpose. Based on the changes of the biological and pharmaceutical indexes mentioned above, the effective parts would be chosen, combining the study on changes of protoberberine type alkaloids, trace elements, volatile oil and gingerols, the material base will be found. At last, the relationship between the changes of biological indexes, pharmaceutical indexes and material base would be discussed to explain the processing mechanism of RC. Through researching, the scientific connotation of processing RC with jinger juice would be clarified, and the research approaches could be used in other similar studies as well.

药性是中药的基本特征，从药性变化角度，结合药效指标变化，探讨与药性药效物质基础变化的相关性，将更助于理解中药炮制目的和作用。采用辛温之性的生姜炮制苦寒之性的黄连，符合传统炮制理论"反制"原则。本课题依据黄连姜制"缓寒，清胃和胃止呕"的炮制目的，通过宏观动物行为学实验、动物微观形态学观察、物质能量指标检测及代谢物组学研究等进行黄连姜制"缓其寒性"的药性生物效应评价；围绕姜黄连"清胃止呕"主要药效，开展抗菌作用、止呕作用、调节胃肠机能、抑制动物胃肠粘膜损伤等方面研究；同时研究小檗碱型生物碱、微量元素、挥发油类成分及非挥发性姜辣素成分变化，并在药性生物效应和药效指标导向下筛选药性药效部位，以明确姜黄连药性药效物质基础；最后，将黄连姜制前后的药性表征-药效-物质基础变化进行谱性-谱效关联分析。通过课题研究，一方面能更深入系统阐明黄连姜制科学内涵，另一方面也为今后类似药物炮制研究提供借鉴思路。

姜制法是一种传统的炮制方法，能够引药入脾经，具有温、散的药性和药效，可以降低中药的毒副作用，至今仍应用较为广泛，并且近年对姜制黄连的研究报道颇多。本课题主要通过对姜黄连炮制前后药性-药效-物质基础的变化来探究姜黄连的炮制机理，并对不同姜汁（生姜汁、干姜汁）对黄连的影响等方面开展研究，以进一步了解姜制对黄连的影响，为阐明姜黄连的“缓寒，增强和胃止呕”炮制机理提供基础。具体方法包括薄层鉴别、HPLC测定生物碱含量、GC-MS测定挥发油含量以及ICP-AES测定微量元素含量等探究其炮制前后化学成分的变化，通过宏观动物学行为、动物微观形态学行为、物质能量指标、代谢组学以及抗菌作用、止呕作用、调节胃肠机能、抑制胃粘膜损伤探究等，探讨姜黄连姜制前后的药性、药效和药效物质基础变化。研究还建立起姜黄连炮制前后的指纹图谱，采用灰色关联度的方法将其物质基础与药效、药性指标进行关联，阐明谱-效-性关系，揭示其炮制机理。得出结论认为，黄连经过姜汁炮制后其寒性大大缓和，且干姜汁在缓和其寒性方面效果比鲜姜汁好。药效方面，黄连经过姜汁炮制后可以增强其抑制胃粘膜损伤作用和止呕作用，保留止泻作用基础上缓和其胃肠动力障碍，并且抗菌效果有了一定程度的增强，鲜姜汁与干姜汁炮制其药效上存在一定差异。通过建立姜黄连炮制前后的“谱-效-性”关系，初步阐明了姜黄连的炮制机理，为黄连的临床和合理应用和提高姜黄连的饮片质量奠定了基础。