离体诱导植物源石杉碱甲的高产克隆系及其机理研究

Alzheimer's disease has become the fourth serious illness for human being. Currently, the most effective medicine in the world to treat Alzheimer's disease should be the drug Huperzine A (Hup-A), which is principally extracted from natural Huperzia serrata. However, insufficient supply of Huperzia serrata plant has become a major bottle neck for new drug development. Through the previous studies,the applicant has established the platform for in vitro culture of the thallus clone of Huperzia serrata,based on the manipulatable principle of plant secondary metabolites This project aims to study the biological response of the secondary metabolism of in vitro thalus to different medium factors and light quality, to evoke the variation in thalus of Huperzia serrata by peroxide factors,and to screen thallus clone lines for high-yeild Hup-A, in order to establish the secondary metabolic engineering system for high yield accumulation of Hup-A by means of in vitro regulation of thallus metabolism,and to reveal the mechanisms by which the influencing factors act on the production of Hup-A from Huperzia serrata in vitro. This work will provide theoretical and technical support for in vitro growth of Huperzia serrata thallus and subsequent Hup-A production.It is anticipated that two or more proprietary intellectual property rights will be obtained at the completion of this project.?This study is theoretically and practically significant either for the resource protection of the Huperzia serrata which is endemic to China or for the application of biotechnology to sustainable production of Huperzine-A.

老年痴呆症已成为人类第四大病魔，石杉碱甲(Huperzine A,Hup-A)制剂是目前国内外最为成功的治疗老年性痴呆症药物，尤其是来源于植物源蛇足石杉的石杉碱甲具有活性高的药效。但此药源匮乏已成为新药研发的最大瓶颈。申请者通过前期工作，建立了离体蛇足石杉叶状体无性增殖系平台，依据植物次生代谢多途径可调控等原理，本项目拟研究离体叶状体次生代谢对不同基质因子和不同光质诱导的生物响应；研究过氧化物因子胁迫蛇足石杉叶状体变异，正向多代筛选高产石杉碱甲应答的叶状体克隆系。最终构建调控离体培养叶状体高产石杉碱甲的技术方法，并揭示相关因子影响离体叶状体生产石杉碱甲的作用机理，为人工生产植物源石杉碱甲资源提供技术和理论支持。本项目实施完成后，预期可获得2项原创性自主知识产权成果，它将对我国特有植物资源蛇足石杉的保护及应用生物技术持续生产石杉碱甲药物资源具有重要的科学意义和应用价值。

老年痴呆症已成为人类第四大病魔，石杉碱甲(Huperzine A,Hup-A)制剂是目前国内外最为成功的治疗老年性痴呆症药物，尤其是来源于植物源蛇足石杉的石杉碱甲具有活性高的药效。本课题应用现代生物技术科学中的多种方法，研究了离体叶状体次生代谢对不同基质因子和不同光质诱导的生物响应；研究了过氧化物因子胁迫蛇足石杉叶状体变异，正向多代筛选高产石杉碱甲应答的叶状体克隆系。构建了调控离体培养叶状体高产石杉碱甲的技术方法，亦揭示了相关因子影响离体叶状体生产石杉碱甲的作用机理。这些研究工作，取得了一些有意义的结果和经验,它将对我国特有植物资源蛇足石杉的保护及应用生物技术持续生产石杉碱甲药物资源具有重要的科学意义和应用价值。