【作者】 惠歌；

【导师】 赵冰；

【作者基本信息】 吉林大学 ， 物理化学， 2010， 博士

【摘要】 药物与生物膜的作用对于药物在体内的代谢过程至关重要,因此研究两者的作用对人们认识了解药效及改善其生物性能具有重要意义。由于拉曼光谱是研究分子结构以及分子内、分子间相互作用的重要方法,差示扫描量热技术(DSC)是研究外加物质对生物膜组分相变影响的有力工具。因此,本论文将光谱技术与热力学技术相结合从分子水平上研究了几种人参皂苷分子(Rb1、Re、Rf、Rg1和Rh2)分别与四种生物膜(DPPC、DMPC、DPPG和DPPE)的作用及其对膜结构的影响,主要研究成果如下：1、利用拉曼光谱研究了五种皂苷分子分别对四种磷脂双层膜的影响。各皂苷分子对不同结构的磷脂双层膜极性头部和疏水性尾部的作用也有差异。在药物浓度逐渐增加的情况下,通过峰值比的变化可以得到皂苷分子对脂双层侧链的作用以及对脂双层膜流动性的影响。2、利用DSC技术对五种皂苷分子分别与四种生物膜的作用进行了检测。在磷脂双层膜从凝胶态到液晶态发生相转变的过程中,通过各热力学参数如主相变温度(Tm)、半峰宽(△T1／2)及相转变焓值(△H)随药物浓度的变化,诠释了各皂苷分子对脂双层热力学属性的影响。3、将皂苷分子与磷脂双层膜作用的拉曼光谱与DSC技术结合起来讨论,在此基础上研究不同皂苷分子对同一磷脂膜作用的影响,以及同一皂苷分子对不同磷脂膜作用的差异,这对于我们进一步了解皂苷分子与细胞生物膜的作用机制,具有重要意义。更多还原

【Abstract】 The interaction between drugs and biomembranes is the first step in the progress of various drugs playing their pharmacodynamics. Thus the research on both interaction is very important and necessary on understanding the efficacy and developing their biological properties. Ginsenosides molecules have become the hotspot topic because of their multi-pharmacutical activities and clinical functions. The study on the influence of ginsenosides on the lipids could provide experimental basises for discussing, realizing and resolving this problem. In this thesis, the differential scanning calorimetry techinique and Raman spectroscopy have been emploied the to study the interaction between five kinds of ginsenoside molecules (Rbl, Re, Rf, Rgl and Rh2) with different category phospholipid liposomes (DPPC, DMPC, DPPG and DPPE). Based on the thermodynamics and from spectroscopy view, the study on the interaction between ginsenoside molecules and biomembranes have been investigated in detailed for the first time on the molecular level. The conclusions are listed as follow:1. During the study on the interactions between five ginsenosides and DPPC, DMPC lipid bilayers respectively, the drug molecules have effects on the polar head group of phospholipids, however, this kind of interaction hasn’t changed the conformation of O-C-C-N+ backbone in the choline group of PC bilayers. The polar head group is still extending parallel to the bilayer surface. Ginsenoside Rbl and Rh2 have significantly increased the fluidity of lipid bilayers. Ginsenoside Re, Rf and Rg1 have no such effects. Moreover, the ginsenosides have showed different degree on perturbating DPPC and DMPC lipisomes. For their different alkyl-chain length, the perturbations of ginsenosides are significantly stronger on DMPC than DPPC.2. In the study of five ginsenosides’ separate affection on the DPPG and DPPE lipid bilayers, Rbl and Rh2 also distinctly decrease their phase-transfer temperature and increased the mobility of acyl chains. Ginsenoside Re, Rf and Rgl have little effects on the fluidity of DPPE and DPPG bilayers. On the difference of molecular structures, the protopanaxadiol ginsenosides have stronger effects on the acyl chains of DPPG and DPPE than the protopanaxtriol ones.3. From the gel phase to liquid crystalline phase transition, the four kinds of phospholipids have differences on the intermolecular attraction because of their different structure. Therefore, the perturbating degree of ginsenosides is different.4. As for the same lipid bilayer, there are various affections because of different ginsenoside molecular structures. This is related to the multi-pharmacutical activities of ginsenosides.更多还原