藏药降压降脂药效成分发现及组方研究

【作者】 李贡宇；

【导师】 张燕玲；

【作者基本信息】 北京中医药大学 ， 中药化学， 2014， 硕士

【摘要】 藏药迄今已有上千年的临床应用历史,其种类仅次于中药。经过数千年的临床应用,以及近几十年来的药理药效研究,其疗效毋庸置疑。目前所收集的藏药中,植物药有2172种、动物药214种、矿物药50多种,其中高原特产藏药86种,西藏临床最常用藏药仅有304种。本文以常用藏药数据库为基础,采用片段搜索、药效团搜索等技术对治疗高血压、高血脂类疾病的藏药有效活性成分进行筛选,结合关联规则发现降压降脂常用藏药药对,开展降压降脂藏药组方研究。主要工作有以下两方面:(1)建立常用藏药数据库。采用MDL ISIS/Base数据库管理系统建立了常用藏药数据库,共收录148味藏药。数据库由藏药信息、化合物信息、文献信息3部分内容构成。其中,藏药信息主要有藏药药性、产地、药理、功效、主治及现代临床应用等1 1个属性;化合物信息主要包含中英文名、分子式、植物来源、理化性质等10个属性;文献信息主要是藏药现代研究方面的参考文献。本数据库能够简单快捷地查询常用藏药的基本信息。(2)藏药降压降脂药效成分发现及组方研究。随着天然药物有效成分提取、分离、纯化及结构研究技术的不断发展,藏药作为天然药物的重要组成部分,其化学成分分析方面的研究成果也获得极大的丰富。本文以常用藏药数据库为基础,利用数据库活性搜索、片段搜索、靶点及结构相似性搜索技术对相关活性成分进行筛选,并追溯其来源藏药;研究结果包括利用数据库活性搜索获得具有明确降压作用的藏药成分53个,来源于36味藏药,具有明确抗高血脂作用的藏药成分13个,涉及22种来源藏药;应用片段搜索、靶点搜索及药效团等方法得到降压藏药活性成分107个,涉及藏药62种;降脂藏药活性成分265个,涉及藏药56种。依靠计算机模拟等技术获得的活性成分、单味药物,存在一定的假阳性,为避免此类问题出现,本研究结合关联规则对藏医治疗高血压、高血脂的用药规律进行分析,以临床实际用药情况为参考确定组方药物,共得到治疗高血压药对6个、高血脂药对8个。在藏药活性筛选和用药规律分析的研究基础上,在藏医降压降脂的理论指导下,探讨藏药组方,最终获得降压组方2个、降脂组方2个。通过本研究为藏药及其化学成分进行了系统的梳理,建立了常用藏药数据库,为藏药数据挖掘搭建了良好的基础平台。对藏药治疗高血压、高血脂的用药规律及物质基础进行了初步探讨,为藏药治疗高血压、高血脂新药开发提供了新的思路。更多还原

【Abstract】 Tibetan medicine has been used for thousands of years.Through thousands years of clinical application and modern pharmacological research in recent decades,the effect of Tibetan medicine is approved.According to the latest survey,there are 2172 herbal medicines,214 animal drugs and over 50 mineral drugs used in Tibetan medicine,but only 304 herbs are used in clinic commonly.In this study,fragment-based searching and pharmacophore-based searching were used basing on Common Tibetan medicine Database to screen active ingredients for anti-hypertension and anti-hyperlipidemia.After this,association rule was applied to discover Tibetan medicine pairs for treating hypertension and hyperlipidemia.Based on the results of two parts,new prescriptions were discussed in this thesis.1.Common Tibetan medicine Construction.MDL ISIS/Base was applied to build a database of Common Tibetan medicine.The database includes 148 Tibetan drugs,and was comprised of drug description data,compound information and literature information.Drug description data mainly contains 11 attributes,such as property,origin,pharmacological effects,function and symptom and clinical application of Tibetan medicine.Compound information includes name in both Chinese and English,molecular formula,physicochemical properties and so on.Literature information is the record of modern research of Tibetan medicine.2.Active ingredients screening and prescriptions design for anti-hypertension and anti-hyperlipidemia.Based on Common Tibetan medicine Database,database searching,fragment-based screening,similarity searching and pharmacophore-based screening were used to screen potential active ingredients with the activity of anti-hypertension and anti-hyperlipidemia.Herbs which contains these active ingredients was retraced.53 potential anti-hypotensive ingredients and 13 potential anti-hyperlipidemia ingredients were obtained by database searching,which extracted from 36 and 22 Tibetan medicines,respectively.By using fragment-,pharmacophore-and targets-based searching techniques there were 107 anti-hypertensive ingredients and 265 anti-hyperlipidemic ingredients obtained,which delt with 62 and 56 Tibetan medicines,respectively.In order to avoid false positive results from simulations,association rule was also applied to analyze the clinical applying rules of Tibetan medicine for anti-hypertension and anti-hyperlipidemia,and 6 anti-hypotensive Tibetan medicine pairs and 8 anti-hyperlipidemia Tibetan medicine pairs were obtained.Combined the results of the active ingredients screening and the association rule analysis,2 anti-hypotensive prescriptions and 2 anti-hyperlipidemia prescriptions were designed in the guidance of Tibetan Medicine theory.更多还原