基于抗补体活性研究丹参抗哮喘的物质基础与作用机制

项目名称： 基于抗补体活性研究丹参抗哮喘的物质基础与作用机制

项目编号： No.81503205

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 宋伟华

作者单位： 苏州大学

项目金额： 18万元

中文摘要： 重型哮喘、激素抵抗型哮喘以中性粒细胞浸润为特征，迄今尚无有效的治疗药物。补体过度激活产物C3a和C5a是重要的中性粒细胞趋化因子。我们的预实验结果显示丹参具有抗补体活性和减轻哮喘小鼠中性粒细胞炎症的作用，但二者是否存在相关性有待进一步探讨。为此，我们提出丹参可能通过抑制补体过度激活这一机制来减轻中性粒细胞炎症。基于以上假说，本项目以体外抗补体活性导向分离活性成分，采用现代波谱技术鉴定单体化合物的结构。在此基础上，利用制备HPLC富集抗补体活性成分以组成新的有效组合物，以中性粒细胞哮喘小鼠作为研究对像，运用HE染色、ELISA、流式细胞术等技术手段研究有效组合物抗哮喘的作用及机制。本项目的研究可以阐明丹参防治中性粒细胞型哮喘的物质基础与作用机制，为治疗重型哮喘、激素抵抗型哮喘提供新的思路和方法。

中文关键词： 抗补体；哮喘；丹参；中性粒细胞

英文摘要： Severe asthma and steroid resistant asthma are characterized by infiltration of neutrophils. There is no effective drug to cure them up to the present. C3a and C5a, decomposed by complement activation, are important in neutrophil chemotactic factor. Our preliminary experimental results showed that the salviae miltiorrhizae radix et rhizoma had anticomplement activity and relieved neutrophil inflammation in asthma mouse, but the mechanism is unkown. So, we hyphothesize that the salviae miltiorrhizae radix et rhizoma relieve neutrophil inflammation by its anticomplement activity. Based on the above hypothesis, chemical investigation will be performed guided by anticomplement activity in vitro and the structures will be elucidated by comprehensive NMR spectroscopy and MS. On this basis, the anticomplement compounds will be enriched by pre-HPLC and combined into a new effective composition. Then, the effective composition anti- asthma activity and mechanism wil be studied on neutrophilic inflammation mouse using HE staining, ELISA and flow cytometer. This project will elucidate the material basis and mechanism of the salviae miltiorrhizae radix et rhizome on anti neutrophilic inflammation asthma, and provide a new way and mean for the treatment of severe asthma and steroid resistant asthma.

英文关键词： anticomeplement;asthma;salviae miltiorrhizae radix et rhizoma ;neutrophil