基于钠离子通道的中药蟾酥镇痛作用药效物质基础和作用机制研究

项目名称： 基于钠离子通道的中药蟾酥镇痛作用药效物质基础和作用机制研究

项目编号： No.81473336

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 田海妍

作者单位： 暨南大学

项目金额： 78万元

中文摘要： 疼痛特别是顽固性疼痛严重影响着患者的健康和生活质量。临床上常用的镇痛药多有效果不明显、耐药性或成瘾性等问题。近年来，靶向钠离子通道的镇痛药物成为研究的热点。这类分子具有镇痛作用强，且不产生明显耐药性和成瘾性的特点。蟾酥为名贵中药，具有消肿止痛之功效，其制剂在临床上常用于缓解牙痛和癌性疼痛等。在前期研究中，我们已从蟾酥中分离鉴定了一系列蟾蜍内酯类化合物，并发现该类化合物具有显著的镇痛活性。初步的作用机制研究表明该类化合物的镇痛活性与钠离子通道的抑制有关，但构效关系和深入的分子作用机制尚不明晰。本项目旨从蟾酥中继续分离蟾蜍内酯类化合物，阐明蟾酥镇痛的药效物质和蟾蜍内酯类化合物镇痛作用的构效关系，用膜片钳、siRNA及基因转染技术研究药效物质抑制钠离子通道的分子机制，以期全面揭示中药蟾酥镇痛作用的科学内涵，并为开发作用于钠离子通道的新型镇痛药提供科学依据。

中文关键词： 药效物质基础；活性成分；作用机制；结构鉴定；构效关系

英文摘要： Pain, especially intractable pain, causes very bad influences on patients' health and daily life.Clinical used analgesic agents usually have not obvious effects, or have deficiencies as drug resistence or addiction.Recent years, investigation of analgesic drugs specifically targeting sodium channel becomes a research hotspot. These molecules showed potent analgesic effects but without drug resistence and addiction.The Chinese Traditonal Medicine (TCM), ChanSu, has obvious analgesic effect,and its TCM preparations were used to treat toothache and cancer pain.In our previous study, we have isolated a series of bufadienolides from ChanSu,and found these compounds showed potent analgesic effects.Moreover,primary mechanism study indicated that sodium channel maybe involved in their analgesic effect.However,the structure-activity relationship and deep molecular mechanism are still unclear.This project aims at isolation of more bufadienolides from ChanSu,clarifying the analgesic material foundation of ChanSu and the structure-analgesic activity relationship of bufadienolides, and investigation of the molecular mechanism of bufadienolides concerning sodium channel.The implementation of the project will fully disclose the scientific connotation of the analgesic effects of ChanSu, and supply scientific basis for developping new analgesic drugs selectively targetting sodium channel.

英文关键词： material foundation of efficacy;active ingredients;mechanism;structural elucidation;structure-activity relationship