基于疏肝指数-化学信息传递研究醋香附疏肝理气机理

Cyperus rotundus, firstly recorded in the "Ming Yi Bie Lu" written by Tao Hongjing of Liang Dynasty, was commended as the manager of Qi disease and the chief of gynecological disease because of its effect in soothing the depressed liver and regulating the menstrual function. Cyperus rotundus has a better soothing effect after processed by vinegar, so the vinegar processed Cyperus rotundus is widely used to cure syndrome of liver-qi stagnation in Traditional Chinese Medicine clinic. The research studies show that the chemical information are different between Cyperus rotundus and vinegar processed Cyperus rotundus, and the processed product has a stronger efficacy. Based on the whole linkage thought of "property-efficacy-application" of Traditional Chinese Medicine before and after processed, we put forward the hypothesis: the change of chemical information of Cyperus rotundus before and after vinegar processed relates to the function of soothing the depressed liver, thus influences vinegar processed Cyperus rotundus's expressing of effect and function representation. According to the thought of "vinegar can guide the Chinese medicine into the liver meridian and help to relieve pain", one of classical Traditional Chinese Medicine processing theory, we will establish the animal model to determine the biochemical index and observe the histopathological features etc. The data of the experimental results will be disposed in order to calculate the "ShuaGan Index", representing the efficacy of soothing the depressed liver. Combined with the chemical information of components in plasam, to certain the internal relationship between "ShuaGan Index and chemical information" and confirm material foundation. Using mass spectrometry technology to lock active ingredient and using microdialysis to research the physiological disposition of active ingredients. By building the internal network of soothing the depressed liver efficiency, the scientific connotation of Vinegar Processing can be further clarified, which could also provide new idea for the mechanism study of vinegar processed Cyperus rotundus of its soothing the depressed liver efficiency.

香附始载于梁o陶弘景的《名医别录》，具有疏肝理气、调经止痛之功效，被誉为"气病之总司，女科之主帅"；香附醋制后疏肝作用增强，在中医临床上广泛用于肝气郁结诸证。课题组前期研究表明：香附醋制前后化学信息存在差异，醋品药效更强。基于中药炮制前后"药性-药效-应用"整体联动的思路，提出假说：香附醋制前后化学信息变化与其疏肝作用存在一定内在关联，进而影响其效应表达和疏肝作用表征。基于中药炮制经典理论之一-"用醋注（入）肝经且资助（止）痛"的思想，建立肝气郁结动物模型，对其进行组织病理学特征观察及生化指标测定等，将所得实验结果的数据降维处理，计算表征疏肝药效的"疏肝指数"；结合其入血成分化学信息，探讨"疏肝指数- - 化学信息"内在关联，明确疏肝物质基础；采用质谱技术锁定疏肝活性成分，利用微透析技术研究其体内过程，构建体内疏肝网络，进一步诠释香附"醋制入肝"的科学内涵，为醋香附疏肝理气机制研究提供新思路。

. 香附具有疏肝理气、调经止痛之功效，醋制后疏肝作用增强，广泛用于肝气郁结诸证。. 为阐释其“醋制增效”机理，课题组采用 GC-MS 法，建立了 3 组香附挥发油的指纹图谱，并采用中药色谱指纹图谱相似度评价软件 A 版进行数据分析。香附各制品相似度良好，得到香附生品共有峰 52 个、参照品 28 个、醋制品 53 个，鉴定了其中 46 个峰，香附炮制后其挥发油成分种类、质量分数均有所变化；以生品为参照，对比参照品和醋制品共有成分，结果醋制品挥发油成分种类保留更为完整，以醋作为炮制辅料科学合理，可起到稳定保护香附挥发油成分的作用；建立HPLC质量控制方法，建立相应指纹图谱，对比分析香附醋制前后化学成分差异；采用慢性不可预见性刺激结合长期皮下注射肾上腺素对大鼠造模，从大鼠体表特征变化、行为学活动和血液流变学 3 个方面指标评价香附醋制前后 “疏肝解郁、活血散瘀”的药效学差异性，结果表明香附生、醋品各剂量组大鼠各项指标均有所改善，等剂量下，醋香附组整体上各指标优于生香附组；采用醋酸致疼痛小鼠模型、缩宫素致痛经小鼠模型、肝郁型血瘀大鼠模型及肝郁型胃肠功能紊乱大鼠模型，测定相关的药理指标，采用SPSS软件结合总评“归一值”法进行多元指标综合评分，筛选出了醋香附疏肝解郁的有效部位。采用双变量相关性分析筛选出与醋香附疏肝作用相关性较大的药效指标，将筛选出的药效指标采用总评“归一值”法计算出各提取部位的“疏肝指数”以评价疏肝效果；以α-香附酮为指标，进行了香附醋制前后胃肠道吸收变化研究，获得香附主要吸收部位，可用以指导制剂设计，结果表明香附醋制后吸收优于生品。. 本项目从化学信息、药效、胃肠吸收动力学多方面研究，结果表明，醋制后，香附化学成分性质、药效、胃肠吸收均有所变化，且醋品药效及胃肠吸收整体优于生品，说明了“醋制增效”的科学性，进行了“疏肝指数”的筛选和计算，为炮制及疏肝解郁药物的研究和药效评价提供思路。.