基于黄芩抗流感病毒研究的中药药效影响因素探讨

【作者】 王雯；

【导师】 孟庆刚；

【作者基本信息】 北京中医药大学 ， 中医基础理论， 2011， 硕士

【摘要】 中医药学具有完整的理论体系,以整体观念和辨证论治指导临床应用,以此为基础的中药药效学具有复杂性和系统性的特点,在与现代医学不断交融以及多学科交叉的进程中亦形成了全方位、多角度的认识。黄芩是经典的常用清热燥湿药,中医诊疗中多用于黄疸泻痢、肺热咳嗽、热病烦渴、胎动不安等症的治疗,现代研究表明黄芩具有抗炎、抗菌、抗病毒、解热、降压、利尿等药理作用,其中所含的黄酮类成分是主要起效部位。而流行性感冒多由病毒引起,与黄芩的治疗作用存在一定的对应关系。本论文首先针对黄芩实验研究现况、抗病毒作用临床应用、以及流行性感冒的研究展开综述,系统梳理与研究目的关联的相关研究情况,为实验和理论的展开奠定基础。在该论文的实验部分,即从抗病毒的角度出发使用流感病毒鼠肺适应株动物模型展开实验。在课题组前期其他的实验中,我们对河北、山西、大连三个产地的黄芩进行了抗流感病毒感染作用的实验研究,结果表明不同来源黄芩提取物均具有良好的抗流感病毒作用,其中尤以河北黄芩水提组效果最佳。随后采用灰色关联度分析方法结合高效液相色谱法进行黄芩谱效关系分析,确定黄芩提取物中黄芩苷、汉黄芩素及黄芩素等成分与抗流感病毒的关系密切,通过对河北黄芩水提组进行含量测定,从而确定了黄芩成分配比物组的组成成分的含量。该实验就河北黄芩水提组与黄芩成分配比物组对流感病毒FM1感染小鼠的死亡保护作用、肺指数、肺组织病毒血凝滴度的影响进行了比较研究,实验结果显示黄芩成分配比物组对FM1所致小鼠有较好的死亡保护作用,能降低感染小鼠的肺指数及病毒血凝滴度,与河北水提组疗效相当,证实黄芩苷、汉黄芩素及黄芩素的合理配比可体现黄芩的药效质量,揭示经典清热燥湿药黄芩在现代应用的意义与支持观点,为同类药物研究提供借鉴。基于此,在理论部分探讨中,首先着眼于对于中药药效学的整体特征认识,在此基础上,层层展开论述。近年对于中药药效的研究多集中在对于中药客体的全方位认识上,同时结合药理学、药物分析学研究方法及其他领域的多学科研究技术,赋予传统中医药学以现代科学内涵,从而展开中药成分与药效的对应关系探讨,这些切入角度客观地反映了中药药效的可控因素,同时可为中药药效评价提供思路。另一方面,在强调对中医药理论的深入挖掘和广泛拓展的基础上,进一步深刻剖析中医临床运用中的认知方式和思维特点在整个临证过程中的重要作用,其思辨性与灵动性与患者神、色、脉等具体表现综合将呈现出太多可能的组合,思维方式对于它们的影响通过医者间接地反映于最终的药效关系。这也是本论文的一个着力点。中药药效的物质基础和作用机制呈现出多样化的趋势,对于药效的评价也应从一个多因素的综合角度来进行考评。选取适宜的评价指标、建立病证统一的动物模型、制定恰当的实验设计都要以临床疗效为考察的最终目的。总而言之,应通过三方有机结合深化对中药及其复方复杂多样的化学成分与机体间相互作用和药效的相关性研究,形成成熟、稳定的药效研究思路。具体到某一类型,以流行性感冒为例,关注其药效学的研究与评价,从中医的角度探讨其不同切入角度及相对成熟的动物模型,并对其表示认可,与本文实验部分呼应。更多还原

【Abstract】 Traditional Chinese medicine have a complete theoretical system, with the overall concept and treatment based on syndrome differentiation to guide the clinical practice. Take this as a fundamental, pharmacy of Chinese materia medica has complexity and systematic characteristics,modern medicine continue to blend in with the multidisciplinary process and has also formed a comprehensive, multi-angle understanding.Radix Scutellariae is a classic medicine which is frequently used to clear heat and remove dampness in the diagnosis and treatment of traditional Chinese medicine, such as jaundice diarrhea, the lung hot cough, the fever bothersome thirsty, the painful fetal movement and so on. Modern research indicates that Radix Scutellariae has anti-inflammatory, antibacterial, antiviral, antipyretic, antihypertensive, diurstic and other pharmacological effects, which contains flavonoids as the main effect spot. The influenza many caused by the virus, therefore, there exist certain corresponding relationships between the therapeutic action of Radix Scutellariae and the virus. The paper first aims at the present experimental study situation of Radix Scutellariae, its antiviral function in clinical practice, as well as the research of the influenza to launches the summary, and systematically summarize the related research situation connect with the research purpose, which lay a foundation for the expand of the theory and experiment.Specific to a particular type, in the case of influenza, paying attention to its pharmacodynamic research and evaluation, investigating its different angles and the relative maturity of the animal model from traditional Chinese medicine point of view and endorse it. In the experimental part of this paper, adapted strain of influenza virus animal model of rat lung was used from the perspective of anti-virus. In other early experiments of our research group, we did anti-influenza virus infection experiments research on Radix Scutellariae from three different origins such as Hebei, Shanxi, Dalian, and the result showed that extractions from different sources all shows good anti-influenza virus effects, which in particular water extraction group of Hebei Radix Scutellariae shows the best effect. Follow by the analysis of Radix Scutellariae spectral activity relationship which use gray correlation analysis method combine with high performance liquid chromatography, ascertain that baicalin, wogonin, baicalein and other ingredients in the extractions of Radix Scutellariae show closely relationship with the anti-influenza virus, the contents of the Radix Scutellariae compositions are confirmed by the determination of the water extraction group of Hebei Radix Scutellariae. In this experiment a comparative study on the effects of the death protective effect to the mice which were infected with by influenza virus FM1, the lung index and lung virus hemagglutination titer between the water extraction group of Hebei Rdix Scutellariae and group of chemical composition Radix Scutellariae property. The result shows that chemical composition of Radix Scutellariae property group has good death protective effect to the mice which were infected with by influenza virus FM1 and has effect on reducing lung index and the hemagglutination titer of virus to the infected mice, which shows same therapeutic effectiveness with the water extraction group of Hebei Radix Scutellariae. This experiment confirms that the reasonable proportion of baicalin, wogonin and baicalein reflects the quality of the classic heat dampness medicine Radix Scutellariae efficacy and reveals the significance and support point view of the radix scutellariae in modern applications, which provides a reference for these similar drugs.In the study of theoretical part, we first focus on the overall pharmacodynamic characteristics of traditional Chinese medicine, and the discussion layers start on this basis. In recent years. research on the efficacy of traditional Chinese medicine more focus on the full range understanding of Chinese medicine objects, combined with the research method in pharmacology, pharmaceutical analysisresearch and other areas of multidisciplinary research techniques, given the traditional Chinese medicine with modern scientific content, and thus expand the traditional Chinese medicine correspondence between composition and efficacy of these cut into the perspective of an objective reflection of the efficacy of Chinese medicine controllable factors, and at the same time provide ideas for the evaluation of efficacy of Chinese medicine. On the other hand, on the basis of emphasis in Chinese medicine theory and extensive expansion, then further profoundly analyse the importance of the cognitive styles and thinking characteristics in the clinical application of traditional Chinese mdicine throughout the clinical process, and its dialectical and flexible quality which will integrated to present too many possible ways of thinking from the patients, spirit, colour, pulse and other specific performance, the impact of their doctors are indirectly reflected in the final efficacy relationship in the meantime. This is another focus of the paper. The material foundation and action mechanism of traditional Chinese medicine efficacy showing diverse trend,so the evaluation of the medicine efficacy should be a combination of factors from from a multi-perspective to conduct the evaluation. Select the suitable evaluation index, establish the disease and syndrome unified animal model, formulate appropriate experimental design nend clinical curative effect as the ultimate goal for investigate. In short, we should organicly combine the three aspects to further the correlative study of traditional Chinese medicine and its compound medicine about the their complex and varied chemical composition which have interaction and efficacy with the organism, so as to form mature and stable medicine efficacy research thought.更多还原