项目名称： 结合靶向表面增强拉曼光谱进行牛蒡子苷元舒张气道平滑肌机制研究

项目编号： No.81503127

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： 赵振营

作者单位： 南开大学

项目金额： 17.9万元

中文摘要： 研究认为气道阻塞性疾病发病过程中的主要效应器为气道平滑肌（ASM），钙离子调节ASM舒缩、ASM细胞膜稳定性影响气道高反应性及气道痉挛。探索具有ASM舒张作用的中药单体的分子靶点及作用机制是中医药现代化与呼吸系统药理相结合的重要研究内容之一。课题组前期研究显示：牛蒡子苷元缓解多种收缩剂所致气管条收缩、降低ASM细胞膜钙离子通道电流、促进钙离子排出和抑制钙离子进入细胞，均提示牛蒡子苷元可能通过降低胞内钙离子浓度和稳定细胞膜而舒张ASM。本项目旨在中医药理论及现代药理学思想指导下，建立豚鼠和大鼠哮喘模型和原代大鼠ASM细胞模型及豚鼠离体气管条张力测定模型，以调节ASM胞内钙离子浓度和稳定细胞膜为切入点，结合SERS拉曼光谱、膜片钳、激光共聚焦等现代先进技术，研究牛蒡子苷元舒张气道平滑肌机制；特别是基于拉曼光谱的药物作用机制研究方法学的建立，将有助于确定药物单体亚细胞水平定位。

中文关键词： 牛蒡子苷元；气道平滑肌；表面增强拉曼光谱；钙离子；离子通道

英文摘要： Scientific evidences reveal airway smooth muscles (ASM) as effectors of airway obstructive diseases (AOD), such as asthma and chronic obstructive pulmonary disease (COPD). It’s one of the key elements to discover ingredients with ASM relaxation effect and the underlying mechanisms in fields of traditional Chinese medicine (TCM). Excitation-contraction coupling with calcium regulation and cellular membrane stabilization can affect hyperresponsiveness and spasm of airways. Our previous studies showed that: arctigenin exhibited relaxation effect on tracheae to different constrictors, and this was related to decreasing cytoplasmic Ca2+ concentration by inhibiting Ca2+ influx partly through L-type calcium channel as well as promoting Ca2+ efflux. However, the detailed molecular mechanism remains elusive. In light of TCM theory as well as modern pharmacology, this project aims at how arctigenin regulating calcium concentration and cellular membrane stabilization. Rat asthma model in vivo and primary ASM cells in vitro shall be established, with adoption of SERS raman spectrum instrument, patch clamp, laser confocal, Western Blot, qRT to explore the potential mechanism how arctigenin relax airway smooth muscles. What’s more, Raman spectroscopy based platform will further contribute to action mechanism research of drugs especially in subcellular levels.

英文关键词： arctigenin;airway smooth muscle;SERS Raman;calcium;ion channel