窄叶鲜卑花中萜类物质的分子印迹聚合物制备及定向分离研究

Sibiraea angustata is a plant of rosaceae family, which had been used as a folk medicine for the treatment of the indigestion and upset stomach by Tibetans for many years, as for, a systematical research on the chemical constituents and their bioactivities from Sibiraea angustata had been done in our group, thirty-one compounds had been identified from the plant for the first time, including sixteen new terpenoids, and these terpenoids showed a significant lipid-lowering activity in preliminary pharmacological experimental. .So, in order to directionally isolate the terpenoids from the plant, the applicant designed a strategy by means of combining Molecular Imprinting Technique (MIT) with Magnetic Nanoparticles (MNPs) to develop a novel terpenoids separating medium, presenting advantages such as highly specific recognition, high adsorption capacity and rapid separation, which will simplify extremely complicated and tedious purification process of terpenoids, as will as solve the problem of seriously hamper the in-depth research of terpenoids..On the basis of the isolation and identification of sixteen active terpenoids from Sibiraea angustata, which will be provided as essential template moleculars for this research, together with the functional monomers, depending on modified magnetic nanoparticles as supporter, to synthesize terpenoids magnetic molecular imprinted core-shell microsphere. Quantitatively control of the MNPs modification and MIPs synthesis will be carried out to dominate the synthesis of terpenoids magnetic nanoparticles molecular imprinted polymers. Electron microscopy (EM), fourier transform infrared (FT-IR), energy dispersive X-ray spectrometer (EDS), and vibrating sample magnetometer (VSM) will be applied to characterize the micromechanism of the resulting composites. Adsorption balance, adsorption thermodynamic model, adsorption isotherm and selective specificity will be also studied to demonstrate the recognition. This research will provide new ideas for application and development of Molecular Imprinting Technique, as well as lay foundations for in-depth study of terpenoids structure-function relationship.

窄叶鲜卑花是蔷薇科植物，藏族民间用于降脂减肥，疗效确切，本课题组对窄叶鲜卑花进行了系统化学及药理研究，先后分离鉴定31个化合物，其中16个新萜类物质，药理研究证明萜类物质是窄叶鲜卑花降脂作用药效物质。因此，本研究拟定向分离萜类物质，采用分子印迹技术和磁性分离技术研究具有高特异性、高吸附性能的新型萜类快速分离介质，简化萜类物质繁琐复杂的纯化过程，解决影响萜类物质深入研究的限速环节。通过前期得到的萜类物质作为模板分子，筛选功能单体，以磁纳米为载体，设计合成萜类磁性表面分子印迹核－壳微球。通过磁纳米功能化修饰及分子印迹体系的定量化控制，实现精准调控萜类磁性印迹微球的合成；通过电镜、光谱、能谱、热重等技术对其微观结构进行表征；通过平衡吸附性能、吸附等温曲线以及竞争性吸附性能研究，揭示其特异性识别。本研究将为分子印迹技术应用和发展提供新思路，为萜类构效关系深入研究奠定基础，为萜类产业化提供科学依据。

首次对藏族民间降脂有效药物窄叶鲜卑花的化学成分及萜类物质分子印迹定向分离进行了系统研究，并对萜类物质的降脂作用、作用机制及构效关系等进行了初步研究。研究内容首创，研究成果达国际领先水平。.① 首次对窄叶鲜卑花进行系统化学成分研究。分离鉴定81个化合物，其中28个新化合物，包括25个新单萜化合物，3个新酚酸化合物。.② 首次采用表面分子印迹技术，选择具有降脂活性的单萜苷Sibiskoside作为模板分子，制备具有核-壳结构的磁性表面功能化分子印迹聚合物，并对其进行结构表征及吸附性能研究，有效实现萜类物质的定向高效制备，减少化学试剂消耗。.③ 首次采用表面分子印迹技术，选择单萜苷的结构类似物京尼平苷作为虚拟模板分子，制备具有核-壳结构的磁性表面功能化虚拟模板分子印迹聚合物，并对其进行结构表征及吸附性能研究，有效实现高效分离富集萜类物质，减少化学试剂消耗。.④ 首次对窄叶鲜卑花的化学成分进行降脂作用及初步构效关系研究，结果表明单萜及三萜化合物等萜类物质具有显著降脂作用，单萜苷元是降脂作用的主要化学片段，糖上的3-羟基-4-甲氧基肉桂酸片段对降脂活性有减弱作用。.⑤ 首次采用实时逆转录聚合酶链和脂质组学方法对萜类物质降脂作用机制进行研究，结果显示其可能通过抑制HepG2细胞中的长链脂肪酸合成，降低细胞中甘油三酯和甘油二酯含量而发挥降脂作用。.⑥ 公开发表学术论文7篇，其中SCI收录论文4篇，中文核心期刊论文3篇。系统报道了窄叶鲜卑花的研究成果。.⑦ 以第一发明人和第一发明单位获批发明专利1项：一种表面功能化磁性纳米分子印迹聚合物的制备方法及其应用，专利号 ZL201811029538.X。.⑧ 培养研究生3名，其中博士研究生1名，硕士研究生2名。.⑨ 参加国内学术会议2次。