蒙药复方述达格-4的药效物质基础及作用机制研究

Mongolian medicine complex prescription of Shudage-4 (Mongolian medicinal Clinical) (Mongolian Medicine Changpu siwei) is a traditional prescription which is used for relieving pain and eliminating breathe heavly in clinical. It is the classical gastropathic prescription. It has been recorded in the Drug Standard of Ministry of Health of the People's Republic of China（Mongolian medicine fascicule）. Based on the combination with healing gastrohelcoma and anti-cancer,this research team has already found the preparation procedure and established the method of quality control of effective part of healing gastrohelcoma and anti-cancer of Mongolian medicine complex prescription of Shudage-4 respectively. We should do the advance research of systemic chemical composition, and to explore the mechanism of action of healing gastrohelcoma of Mongolian medicine complex prescription of Shudage-4 acording to build gastrohelcoma pathological model, to improve the quality standard.To study and research the relationship of HPLC fingerprint- effect of effective part of healing gastrohelcoma of Mongolian medicine complex prescription of Shudage-4 acording to multiple linear regression analysis in carry out the experiment of compatibility HPLC finger print of effective part matching to the gastrelcoma pathological model .To determine the active components group of healing gastrohelcoma, to identify the chromatographic peaks of active components acording to the method of adding control article,then determine the active component.Carry out the study and research of mechanism of action of anti-cancer in vivo of active components or active components group after aiming directly at antineoplasmic activity part of vitro.All in all, we can draw the conclusion based on the project research to explain the pharmacodynamic action substance foundation and mechanism of action of healing gastrohelcoma and anti-cancer of Mongolian medicine complex prescription of Shudage-4.This study plays an typical example role in modernization of Mongolian medicine.

蒙药复方述达格-4（菖蒲四味）是蒙医临床上常用的消喘止痛传统配方，蒙医临床治疗胃病的经典方剂，被收载于《中华人民共和国卫生部药品标准(蒙药分册)》。本课题在已完成结合治疗胃溃疡、抗肿瘤实验基础上分别建立蒙药复方述达格-4治疗胃溃疡、抗肿瘤有效部位制备工艺及质量控制方法，拟进一步对述达格-4进行系统的化学成分研究；建立胃溃疡病理模型，探索蒙药复方述达格-4治疗胃溃疡的作用机制；完善其质量标准；通过对有效部位配伍HPLC指纹图谱配合胃溃疡病理模型实验，采用多元线性回归分析，研究述达格-4有效部位的谱-效关系，确定其治疗胃溃疡的有效成分群；采用添加对照品的方法，指认有效成分色谱峰，确定有效成分。并针对述达格-4抗肿瘤活性部位及体外抗肿瘤活性强的有效成分群或有效成分进行体内抗肿瘤作用机制研究。通过本课题的研究，阐释述达格-4治疗胃溃疡、抗肿瘤的药效物质基础、作用机制。对推动蒙药现代化具有典型意义。

蒙药复方述达格-4是蒙医临床上常用的消喘止痛传统配方，蒙医临床治疗胃病的经典方剂，被收载于《中华人民共和国卫生部药品标准(蒙药分册)》。由石菖蒲、木香、高良姜、紫硇砂四味药组成, 具镇“巴达干赫依”，消喘止痛作用，用于膈肌痉挛、胸闷气短、胸肋刺痛、消化不良。.本课题对蒙药复方述达格-4有效部位进行化学成分研究: 从蒙药复方述达格-4中共分离得到33个单体化合物，鉴定了其中28个。其中13个为首次从述达格-4分得。.分别建立了小鼠乙醇致胃溃疡动物模型、应激反应致胃溃疡模型和大鼠醋酸烧灼型胃溃疡模型,并分别进行SOD、MDA和NO含量测定、溃疡指数和抑制率的计算以及石蜡切片HE染色对胃溃疡组织进行了病理检查。对其抗肿瘤活性进行了研究。针对述达格-4体外抗肿瘤活性强的有效成分群进行了体内抗肿瘤作用机制研究。.完善了其质量标准: 根据有效成分研究的结果，从分离得到的化学物质中筛选针对药效更专属的对照品，达到质量标准的提升。建立了述达格-4药材和有效部位的薄层层析的定性鉴别方法，采用薄层色谱法对蒙成药中的山奈素、高良姜素、熊果酸进行了薄层色谱鉴别。建立有效部位中总类成分（总黄酮、总苯丙素、总内酯）和指标性成分（高良姜素、山奈素、高良姜素-3-甲醚、1-苯基-7-(3-甲氧基-4-羟基)苯基-5-醇-3-庚酮）的含量测定方法。.完善了已建立蒙药复方述达格-4有效部位的HPLC指纹图谱，确定了有效组分配伍HPLC指纹图谱共有指纹峰的来源。通过对有效部位配伍HPLC指纹图谱配合小鼠乙醇致胃溃疡动物模型实验，采用多元线性回归分析，并通过建立蒙药复方达格-4体内外特征图谱，归属并鉴定其体外化学成分及体内吸收入血成分。确定了其治疗胃溃疡的有效成分群。采用添加对照品的方法，指认有效成分色谱峰，确定有效成分。进行了网络药理学的研究，建立了蒙药复方达格-4化学成分-靶点-疾病网络节点图及相关信号通路。通过本课题的研究，阐释了述达格-4治疗胃溃疡的药效物质基础、作用机制。