【作者】 潘学诗；

【导师】 甘礼华；

【作者基本信息】 同济大学 ， 物理化学， 2008， 硕士

【摘要】 生物膜在生命过程中起着十分重要的作用。由于生物膜的组成的不确定性和结构的复杂性,对模拟生物膜的研究已日益受到关注。双层类脂膜既具备生物膜基本构架,又克服了生物膜的复杂性,是研究生物膜体系理想的简化模型。近年来,双层类脂膜作为生物膜模型的研究得到了人们的广泛重视,在药物的药理机制探索、生物膜功能研究以及生物传感器等领域展现出广阔的发展前景。考虑到左氧氟沙星和异丙酚两种药物的药理机制都可能与它们对细胞膜的影响有关,本论文选取这两种药物为研究对象,从分子水平上探讨了它们与双层类脂膜的作用机制,同时考虑到双层类脂膜和真实生物膜的稳定性差异,从成膜基底和成膜液组成着手探索了提高双层类脂膜稳定性的方法,使之更加接近真实生物膜。在不同表面形貌的金属基底上,以不同组成的成膜液制备了支撑的双层类脂膜,用循环伏安法和交流阻抗法表征了其电流、电阻和电容等电化学参数,探讨了这几种因素对双层类脂膜性质的影响及其机制。用循环伏安法和交流阻抗法表征了左氧氟沙星和异丙酚对不同组成的双层类脂膜的电流、电阻、电容等电化学参数的影响,并探讨了它们对膜的作用机理。本论文得到的主要结论如下:（1）金属基底的表面形貌和端面面积对双层类脂膜的制备有很大影响,平整的表面形貌有助于增加双层类脂膜在变薄过程中的稳定性。金属基底的端面面积过大会增加成膜过程中的膜发生破溃的可能性,降低双层类脂膜的稳定性,但较大的端面面积有利于获得面积较大的双层类脂膜,减少实验误差。在能得到稳定的双层类脂膜的前提下,制备时应尽量选择端面面积较大的金属基底。（2）电化学测试结果表明,成膜液中卵磷脂含量为5%时能够获得成膜情况最佳、膜电阻最小的双层类脂膜。双层类脂膜中胆固醇含量的增加会增加双层类脂膜对电子的阻碍作用,胆固醇与卵磷脂比例为4:1的双层类脂膜最适合用于模拟真实生物膜。（3）左氧氟沙星能与双层类脂膜发生作用,使双层类脂膜的循环伏安电流增大。左氧氟沙星溶液的浓度越大,对双层类脂膜产生影响越强烈。这可能是由于左氧氟沙星3-位有带负电荷的羧基,与卵磷脂分子中带正电荷的极性头-N⁺（CH₃）₃发生作用,使膜中卵磷脂分子紧密的定向排列遭到破坏,双层类脂膜结构变得松散,膜上卵磷脂发生小块脱落,产生微孔。（4）异丙酚上的酚羟基能与双层类脂膜发生作用,使双层类脂膜的膜电阻减小,对电子的阻碍作用降低,通透性增加。异丙酚浓度越大,对双层类脂膜的影响越强烈。这可能是由于酚羟基中的芳环可作用于卵磷脂分子亲油端中的碳-碳双键,同时酚羟基可以与卵磷脂中的酰胺基形成氢键。这两种作用使卵磷脂分子的两亲性被破坏,双层类脂膜发生小块脱落或产生微孔。胆固醇的存在使得双层类脂膜的卵磷脂分子之间结合较紧密,受异丙酚影响较小,胆固醇的存在对保持细胞膜的正常功能和形态起到了重要作用。更多还原

【Abstract】 The biomembrane play rather important role in the life process. Because of the complication of the biomembrane’s structure and components, it is paid more and more attentions gradually. The bilayer lipid membranes （BLM） have the basic framework of biomembrane without the complication of biomembrane, which are great-simplified model for the research of biomembrane. Presently, the BLM become the focus of researches as the model of biomembrane, which show great prospects in the research of pharmacological mechanisms of medicines, the function of bimembrane and the bisensors.Taking account of that the pharmacological mechanisms of levofloxacin and propofol may have relationship with their influences to the biomembrane, we have picked the two medicines to be our objectives, which’s influence to the BLM had been studied. Also, considering the differences between real biomembrane and the BLM, we have studied how to improve the stability of the BLM by mediating the substrates and the film-forming liquid. We try to make the BLM to be similar with real biomembrane, though our study.We have fabricated the supported-BLM（s-BLM） in several kinds of substrates with different surface morphology and characterized their current, resistances and capacitances with Cyclic Voltammetry（CV） and AC Impedance. We have also studied the influences that these factors exerted on the s-BLM. We have also characterized the changes that the different volume of levofloxacin and propofol exerted on the current, resistances and capacitances of the s-BLM. And we have study the mechanisms of all the influences above. The Conclusions are:1. The surface morphology and the area of the cutting plane exerts great influences on the fabrication of s-BLM. Good surface morphology would help to improve the stability of s-BLM in the process of its thinning. The cutting plane with too large area would improve the risk of collapse during its thinning, and also reduce the stability of the s-BLM. But larger areas are helpful to getting larger s-BLM and reducing errors. So we should choose substrates with larger area of cutting plane with the prerequisite that we can get steady s-BLM.2. The results of electrochemistry tests indicate that the s-BLM with best conditions and smallest resistance using the film-forming liquid of 5% lecithin. The resistance to the electron will increase with the increase of the proportion of cholesterol in the s-BLM increase. The best rate to simulate the real biomembrane is 4:1.3. The results of electrochemistry tests indicate that the levofloxacin will enlarge the current getting through the s-BLM. The reason may be that the carboxyl in the levofloxacin with negative charge can act on the -N⁺（CH₃）₃ polar head of the lecithin in the s-BLM, which can break the directional arrangement of lecithin, and loose the structure of s-BLM, so that the lecithin on the s-BLM will fall off from the frame work, which can induce the hole in the s-BLM.4. The phenolic hydroxyl on the propofol can act on the s-BLM, which can induce the deduction of the s-BLM’s resistances to the electrons. The s-BLM will became more easily to be gotten through by electrons. Higher concentration of propofol can induce more intensive reaction. The reason may be that the aromatic ring in phenolic hydroxyl act on the double bond between carbon atoms and also can form H-bond with amide group, which can break the amphiphilic property of the lecithin, which will induce the lecithin to fall off from the frame work. Then, there will be some holes in the s-BLM. The presence of cholesterol in s-BLM will close the combination between lecithin so that the s-BLM will be less influenced. So the presence of cholesterol can maintain the function and the configuration of biomembrane.更多还原