左氧氟沙星/异丙酚对支撑双层类脂膜的影响研究
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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~+(CH_3)_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。
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~+(CH_3)_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.
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~+(CH_3)_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。
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~+(CH_3)_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.
引文
铩颷1]张金莲,吴振斌.水环境中生物膜的研究进展[J].环境科学与技术,2007,30(11):102-106
[2]黄鹏,赵庆良,胡万里,张瑛瑛.移动床生物膜反应器处理回用PVC母液废水[J].黑龙江大学自然科学学报,2007,24(5):634-638
[3]张宇锋,王黎,侯新朴.膜上相互作用对平板双分子层脂膜电性质的影响[J].生物物理学报,2000,16(4):694-700
[4]朱彩莲,李鸣宇,叶冬霞.比较6种口腔材料对体外生物膜形成的影响[J].口腔材料器械,2007,16(4):175-177
[5]邵圣文,樊瑜,顾红光,邵华,张志智,王文琴.铜绿假单胞菌生物膜与下呼吸道反复感染关系[J].中国公共卫生,2007,23(11):1366-1367
[6]H.T.Tien,Angelica L.Ottova.The lipid bilayer concept and its experimental realization:from soap bubbles,kitchen sink,to bilayer lipid membranes[J].ELSEVIER,2001,189:83-117
[7]R.Hooke,Royal Society Meeting,The History of the Royal Society of London,T.Birch(Ed.),1672,3(29A):1757
[8]H.T.Tien,A.L.Ottova.Membrane Biophysics:As Viewed From Experimental Bilayer LipidMembranes(planar lipid bilayers and spherical liposomes)[J].Elsevier,2000:648
[9]A.Ottova,V.Tvarozek,J.Racek,J.Sabo,W.Ziegler,T.Hianik.Self-assembled BLM:biomembrane models and biosensor applications[J].Supramol.Sci,1997,4:101.
[10]E.Gorter,F.Grendel.On bimolecular layers of lipids on the chromocytes of the blood[J].Exp.Med,1925,41:439
[11]P.Fishman.Proceedings of the Symposium on the Plasma Membrane[M].New York City:American Heart Association and New York Heart Association.1962,26:5
[12]P.Mueller,D.O.Rudin,H.T.Tien,W.C.Wescott.Reconstitution of cell membrane structurein vitro and its transformation into an excitable system[J].Nature 1962:2211-217.
[13]P.Mueller,D.O.Rudin,H.T.Tien,W.C.Wescott.Reconstitution of cell membrane structurein vitro and its transformation into an excitable system[J].J.Phys.Chem,1963,67:534
[14]J.D.Robertson.Unit membrane hypothesis[J].Cell Biol,1981,91:189
[15]M.Kerker.Surface Chemistry and Colloids[M].MTP International Review of Science A.D.Butterworths,London:Buckingham(Consultant Ed.).1972:7,Chapters 1 and 2
[16]H.T.Tien,A.L.Ottova.Membrane Biophysics:As Viewed From Experimental Bilayer LipidMembranes(planar lipid bilayers and spherical liposomes)[J].Elsevier,2000:1-648
[17]李自双,黄兰,张显全,蔡绍皙,吴云鹏.心肌梗塞病患者红细胞膜粘弹性的实验研究.中国生物医学工程学报,2000,3(19):生物力学.
[18]毕只初,H.T.Tien,A.L.Ottova.类脂双层(BLM)概念及其实验进展-BLM的40年[J].生物化学与生物物理进展,2001,28(4):447-454
[19]H.T.Tien,Ottov A L.From self-assembled bilayer lipid membranes(BLM)to supported BLM on metal and gel substrates to practical applications[J].ELSEVEIR,1999,149:217-233.
铩颷20]周晴中,何艳梅.模拟生物膜的聚合单层、双层和脂质体[J].大学化学,1994,9(1):25-30.
[21]Angelica Ottova,H.T.Tien.The 40th anniversary of bilayer lipid membrane research[J].Bioelectrochemistry[J].ELSEVEIR,2002,56:171-173.
[22]Singer S.J.G.L.Nicolson.The fluid mosaic model of the structure of cell membranes[J].Science,1972,175:720-731.
[23]H.T.Tien,Zdzislaw Salamon.Formation of self-assembled lipid bilayers on solidsubstrates[J].Bioelectrochemistry and Bioenergetics[J].ELSEVEIR,1989,22:211-217.
[24]Kco S P,Bayer A S,Kagan B L,et.Membrane permeabilization by thrombin-inducedplatdet micmbicidal protein lisrrtoduhted by voltage polarity and trte-fitnde Infect Innnun[J].ELSEVEIR,1999,67(5):2475-2481
[25]Xiandao Lu,Angelica Leitmannova Ottova,H.Ti Tien.A new method for forming andstudying planar bilayer lipid membranes[J].Bioeletrochemistry and Bioenergetics,1996,39:285-289.
[26]H.T.Tien,Angelica L.Ottova.From self-assembled bilayer lipid membranes(BLM)tosupported BLM on metal and gel substrates to practical applications Colloids and Surfaces A:Physicochemical and Engineering Aspects[J].ELSEVEIR,1999,149:217-233.
[27]H.Gao,G.-A.Luo,J.Feng,H.T.Tien,A.L.Ottova,Photoelectric property of bilayer lipidmembranes self-assembled on ITO substrate[J].Electroanal.Chem.2001,496:158-161.
[28]高宏,罗国安,冯军,H.T.Tien,A.L.Ottova.自组装ITO/双层磷脂膜的制备及其光电行为研究[J].高等学校化学学报,2001,3(22):376-379.
[29]M.Mountz,H.T.Tien,Photoeffects of pigmented lipid membranes in a micropourous filter[J],Photochem.Photobiol[J].ELSEVEIR,1978,28:395-401.
[30]M.Thompson,R.B.Lennox,R.A.McCleland.Structure and electrochemical properties ofmicrofiltration filter-lipid membrane systemsAnal[J].Chem.,1982,54:76-81.
[31]H.Yoshikawa,H.Hayashi,T.Shimooka,H.Terada,T.Ishi.Stable Phospholipid MembranesSupported on Porous Filter Paper[J].Biochem.Biophys,1987,145:1092-1097.
[32]C.G.Siontorou,A.M.Oliveira Brett,D.P.Nikolelis.Evaluation of a.glassy carbon electrodemodified by a bilayer lipid membrane with.incorporated DNA[J].Talanta,1996,43:1137-1144.
[33]Z.L.Cheng,E.K.Wang,X.R.Yang.Capacitive detection of glucose using molecularlyimprinted polymers[J].Biosens.Bioelectron,2001,16(3):179-185.
[34]P.Krysin' ski,A.Zú ebrowska,A.Michota,J.Bukowska,L.Becucci,M.R.MoncellTethered Mono- and Bilayer Lipid Membranes on Au and Hg[J].Langmuir,2001,17:3852-3857.
[35]H.T.Tien,Samuel H Wurster,Angelica L Ottova.Electrochemistry of supprted bilayer lipidmembranes:background and techniques for biosensor development[J].Bioelectrochemistry andBilenergetics,1997,(42):77-94.
[36]H.T.Tien.Bilayer Lipid Membrane(BLM)Theory and Practice[M].New York:MarcelDekker Inc,1974.
铩颷37]Sijbren.Otto,Vaclav.Janout,Audrey.F.DiGiorgio,Malinda.C.Young,Steven.L.Regen.Detection of Nonideal Mixing of Phospholipids in Fluid Bilayers[J].Am.Chem.Soc,2000,122:1200-1204.
[38]H.T.Tien,Zdzislaw Salamon.Cyclic voltammetry studies of biomembranes deposited onplatinum by self assembly[J].B ioelectrochemestry and Bioenergetics,1989,22:211-218.
[39]刁鹏,姜殿禄,崔晓莉,顾登平,童汝亭.一种制备铂支撑自组装双层类脂膜新方法[J].电化学,1999,5(3):288-293.
[40]王建国,江黎丽,惠飞,杨薇薇,吕慧,孙巧花.脱氧胆酸钠与支撑磷脂双层膜作用的电化学研究[J].化学学报,2007,65(3):239-245.
[41]王建国,滕人瑞,汪尔康.杂多酸K_7Fe_3 P_2W_(17)O_(62)H_2对硫醇一磷脂杂化双层膜通透性的影响[J].化学学报,2004,59(12):2138-2142.
[42]马勇,霍俊杰,惠飞,王建国,韩正波,臧树良.Keggin型杂多酸H3 PMo_(12)O_4对磷脂双层膜电化学行为的影响[J].辽宁大学学报,2006,33(2):97-100
[43]刘妍,陈艳艳,靳刚.硅基片上的自组装双层磷脂分子膜层[J].纳米器件与技术.2007,4(1):22-26
[44]Yan Li Zhang,James Dunlop,Thai Phung,Angelica Ottova,H.T.Tien.Supported bilayerlipid membranes modified with a phosphate ionophore[J].ELSEVEIR,2006,21:2311-2314
[45]Yu-Feng Zhang,Xin-Hou,Gang Wu,Rong-Chang Li,Xin-Wen Qiao,H.Ti Tien.Study onselectivity of permeating chiral complexes in bilayer lipid membranes(BLM)[J].ELSEVEIR,1999,1:238-241.
[46]T.Hianik,J.Dlugopolsky,M.Gyeppessova,B.Sivak,H.T.Tien,A.Ottova-Leitmannova.Stabilization of bilayer lipid membranes on solid supports by trehalose[J].ELSEVEIR,1996,39:299-302.
[47]A.Tripathy,H.T.Tien,Angelica L.Ottova.A study of reconstituted anion charmels usinglipid bilayers[J].ELSEVEIR,1998,44:183-199.
[48]Li Wang,Xin-Pu Hou,Angelica Ottova,H.T.Tien.Receptor-ligand interactions in areconstituted bilayer lipid membrane[J].ELSEVEIR,2000,2:287-289.
[49]赵艳.方炎.双层类脂膜成膜过程的电化学方法研究[J].电化学,2004,10(1):70-74.
[50]陈华丽,韦云隆,刘盛平.碘修饰的S-BLM生物传感器研究[J].汕头大学学报,2003,18(1):19-23
[51]高宏,罗国安.双层磷脂膜的电化学性质及其在生物传感器中的应用[J].分析科学学报.2002,18(1):70-74.
[52]Jianguo Wang,Li Wang,Shaoqin Liu,Xiaojun Han,Weimin Huang,Erkang Wang.Interaction of K Fe3qP W O H with supported bilayer lipid[J].ELSEVEIR,2003,106:31-38
[53]韩晓军,宋永海,昊正岩,张柏林,汪尔康.钙离子对支撑磷脂膜离子通道行为的诱导作用[J].高等学校化学学报.2001,22(3):12 1298-1300.
[54]Kinji Asaka,H.T.Tien,Angelica Ottova.Voltammetric study of charge transfer acrosssupported bilayer lipid membranes(s-BLM)[J].ELSEVEIR,1999,40:27-37.
[55]蔡红,王斌,张占军,蔡生民.不锈钢支撑双层类脂膜离子传感器的电化研究与应用. 应用化学[J].2003,20(4):307-311.
铩颷56]蔡红,王斌,张占军.C_(60)修饰的s-BLM离子传感器的研究与应用[J].安徽大学学报,2003,27(1):84-88.
[57]Kinji Asakaa,Angelica Ottovab,H.T.Tien.Mediated electron transfer across supportedbilayer lipid membrane(s-BLM)[J].ELSEVEIR,1999,354:201-207.
[58]H.T.Tien,Lei-Guang Wang,Xing Wang,Angelica L.Ottova.Electronic processes insupported bilayer lipid membranes(s-BLM)containing a geodesic form of carbon(fullerene C60)[J].ELSEVEIR,1997,43:161-167.
[59]程洪艳,胡颖,王燕平,方炎.C_(60)衍生物修饰的固体支撑双分子层磷脂膜(s-BLM)分子器件的电化学和拉曼光谱研究[J].光谱学与光谱分析.2002 22(3):403-406.
[60]Jian-Shan Yea,Angelica Ottovab,H.T.Tien,Fwu-Shan Sheu.Nanostructured platinum-lipidbilayer composite as biosensor[J].ELSEVEIR,2003,59:65-72.
[61]H.T.Tien,Samuel H.Wurster,Angelica L.Ottova.Electrochemistry of supported bilayerlipid membranes:background and techniques for biosensor development[J].ELSEVEIR,1997,42:77-94.
[62]J.Sabo,A.Ottova,G.Laputkova,M.Legin,L.Vojcikova,H.T.Tien.A combined AC-DCmethod for investigating supported bilayer lipid membranes[J].ELSEVEIR,1997,306:112-118.
[63]扈显琦,梁成浩.交流阻抗技术的发展与应用[J].腐蚀与防护,2004,25(2):57-60
[64]程志亮,杨秀荣.电化学交流阻抗技术表征自组装多层膜[J].分析化学,2001,29(1):6-10.
[65]高宏,罗国安,冯军.硫醇.磷脂混合双层膜的电化学性质及其与蜂毒素的相互作用研究[J].化学学报,2001.59(2):220-223.
[66]欧阳钟灿,刘寄星.从肥皂泡到液晶生物膜[M].长沙:湖南教育出版社,1995.
[67]崔大付,张兆田,熊小芸,徐建华.生物电子学的研究与发展[J].中国科学基金,2004,4:205-211.
[68]崔生辉,李景云,马越.细菌对氟喹诺酮类药物的耐药机制[J].中国药房,2007,18(14).
[69]赵艳,方炎.BLM成膜液中胆固醇与卵磷脂相互作用的光谱学研究[J].光散射学报,2004,16(1):79-83
[70]Milhaud J,Ponsinet V,Takashi M,Michels B.Interactions of the drug amphotericin B withphospholipid membranescontaining or not ergosterol:new insight into the role of ergosterol[J].Biochimica et Biophysica Acta,2002,95:1558
[71]杨运煌.血清中分子间相互作用的NMR研究[D].中国科学院武汉物理与数学研究所.2004
[72]张晋蓉,林财珠,杨锡馨,吕凯荣,盛国庆,戴体俊.异丙酚对PC12细胞和脂质体膜流动性的影响[J].中国临床药理学与治疗学.2003 8(2):129-132.
[73]盛国庆,张晋蓉,戴体俊,蒲小平,李长龄.异丙酚对PC12细胞膜流动性及[Ca~(2+)]的影响[J].中国药理学通报,2002,18(3):264-266.
[74]张德林.茶多酚产品的主要成分及抗油脂氧化机理的研究报告[J].广州食品工业科技,1993,3:27-31.
铩颷75]宋玉光,孙健,Nohl Hans,刘扬.几种含羟基化合物对红细胞膜流动性的影响[J].波谱学杂志.2005,22(4):351-355.
[76]谢祖芳,夏金虹,晏全.聚酰胺吸附硝基苯酚的热力学与机理探讨[J].化工技术与开发,2003,32(2):10-13.
[2]黄鹏,赵庆良,胡万里,张瑛瑛.移动床生物膜反应器处理回用PVC母液废水[J].黑龙江大学自然科学学报,2007,24(5):634-638
[3]张宇锋,王黎,侯新朴.膜上相互作用对平板双分子层脂膜电性质的影响[J].生物物理学报,2000,16(4):694-700
[4]朱彩莲,李鸣宇,叶冬霞.比较6种口腔材料对体外生物膜形成的影响[J].口腔材料器械,2007,16(4):175-177
[5]邵圣文,樊瑜,顾红光,邵华,张志智,王文琴.铜绿假单胞菌生物膜与下呼吸道反复感染关系[J].中国公共卫生,2007,23(11):1366-1367
[6]H.T.Tien,Angelica L.Ottova.The lipid bilayer concept and its experimental realization:from soap bubbles,kitchen sink,to bilayer lipid membranes[J].ELSEVIER,2001,189:83-117
[7]R.Hooke,Royal Society Meeting,The History of the Royal Society of London,T.Birch(Ed.),1672,3(29A):1757
[8]H.T.Tien,A.L.Ottova.Membrane Biophysics:As Viewed From Experimental Bilayer LipidMembranes(planar lipid bilayers and spherical liposomes)[J].Elsevier,2000:648
[9]A.Ottova,V.Tvarozek,J.Racek,J.Sabo,W.Ziegler,T.Hianik.Self-assembled BLM:biomembrane models and biosensor applications[J].Supramol.Sci,1997,4:101.
[10]E.Gorter,F.Grendel.On bimolecular layers of lipids on the chromocytes of the blood[J].Exp.Med,1925,41:439
[11]P.Fishman.Proceedings of the Symposium on the Plasma Membrane[M].New York City:American Heart Association and New York Heart Association.1962,26:5
[12]P.Mueller,D.O.Rudin,H.T.Tien,W.C.Wescott.Reconstitution of cell membrane structurein vitro and its transformation into an excitable system[J].Nature 1962:2211-217.
[13]P.Mueller,D.O.Rudin,H.T.Tien,W.C.Wescott.Reconstitution of cell membrane structurein vitro and its transformation into an excitable system[J].J.Phys.Chem,1963,67:534
[14]J.D.Robertson.Unit membrane hypothesis[J].Cell Biol,1981,91:189
[15]M.Kerker.Surface Chemistry and Colloids[M].MTP International Review of Science A.D.Butterworths,London:Buckingham(Consultant Ed.).1972:7,Chapters 1 and 2
[16]H.T.Tien,A.L.Ottova.Membrane Biophysics:As Viewed From Experimental Bilayer LipidMembranes(planar lipid bilayers and spherical liposomes)[J].Elsevier,2000:1-648
[17]李自双,黄兰,张显全,蔡绍皙,吴云鹏.心肌梗塞病患者红细胞膜粘弹性的实验研究.中国生物医学工程学报,2000,3(19):生物力学.
[18]毕只初,H.T.Tien,A.L.Ottova.类脂双层(BLM)概念及其实验进展-BLM的40年[J].生物化学与生物物理进展,2001,28(4):447-454
[19]H.T.Tien,Ottov A L.From self-assembled bilayer lipid membranes(BLM)to supported BLM on metal and gel substrates to practical applications[J].ELSEVEIR,1999,149:217-233.
铩颷20]周晴中,何艳梅.模拟生物膜的聚合单层、双层和脂质体[J].大学化学,1994,9(1):25-30.
[21]Angelica Ottova,H.T.Tien.The 40th anniversary of bilayer lipid membrane research[J].Bioelectrochemistry[J].ELSEVEIR,2002,56:171-173.
[22]Singer S.J.G.L.Nicolson.The fluid mosaic model of the structure of cell membranes[J].Science,1972,175:720-731.
[23]H.T.Tien,Zdzislaw Salamon.Formation of self-assembled lipid bilayers on solidsubstrates[J].Bioelectrochemistry and Bioenergetics[J].ELSEVEIR,1989,22:211-217.
[24]Kco S P,Bayer A S,Kagan B L,et.Membrane permeabilization by thrombin-inducedplatdet micmbicidal protein lisrrtoduhted by voltage polarity and trte-fitnde Infect Innnun[J].ELSEVEIR,1999,67(5):2475-2481
[25]Xiandao Lu,Angelica Leitmannova Ottova,H.Ti Tien.A new method for forming andstudying planar bilayer lipid membranes[J].Bioeletrochemistry and Bioenergetics,1996,39:285-289.
[26]H.T.Tien,Angelica L.Ottova.From self-assembled bilayer lipid membranes(BLM)tosupported BLM on metal and gel substrates to practical applications Colloids and Surfaces A:Physicochemical and Engineering Aspects[J].ELSEVEIR,1999,149:217-233.
[27]H.Gao,G.-A.Luo,J.Feng,H.T.Tien,A.L.Ottova,Photoelectric property of bilayer lipidmembranes self-assembled on ITO substrate[J].Electroanal.Chem.2001,496:158-161.
[28]高宏,罗国安,冯军,H.T.Tien,A.L.Ottova.自组装ITO/双层磷脂膜的制备及其光电行为研究[J].高等学校化学学报,2001,3(22):376-379.
[29]M.Mountz,H.T.Tien,Photoeffects of pigmented lipid membranes in a micropourous filter[J],Photochem.Photobiol[J].ELSEVEIR,1978,28:395-401.
[30]M.Thompson,R.B.Lennox,R.A.McCleland.Structure and electrochemical properties ofmicrofiltration filter-lipid membrane systemsAnal[J].Chem.,1982,54:76-81.
[31]H.Yoshikawa,H.Hayashi,T.Shimooka,H.Terada,T.Ishi.Stable Phospholipid MembranesSupported on Porous Filter Paper[J].Biochem.Biophys,1987,145:1092-1097.
[32]C.G.Siontorou,A.M.Oliveira Brett,D.P.Nikolelis.Evaluation of a.glassy carbon electrodemodified by a bilayer lipid membrane with.incorporated DNA[J].Talanta,1996,43:1137-1144.
[33]Z.L.Cheng,E.K.Wang,X.R.Yang.Capacitive detection of glucose using molecularlyimprinted polymers[J].Biosens.Bioelectron,2001,16(3):179-185.
[34]P.Krysin' ski,A.Zú ebrowska,A.Michota,J.Bukowska,L.Becucci,M.R.MoncellTethered Mono- and Bilayer Lipid Membranes on Au and Hg[J].Langmuir,2001,17:3852-3857.
[35]H.T.Tien,Samuel H Wurster,Angelica L Ottova.Electrochemistry of supprted bilayer lipidmembranes:background and techniques for biosensor development[J].Bioelectrochemistry andBilenergetics,1997,(42):77-94.
[36]H.T.Tien.Bilayer Lipid Membrane(BLM)Theory and Practice[M].New York:MarcelDekker Inc,1974.
铩颷37]Sijbren.Otto,Vaclav.Janout,Audrey.F.DiGiorgio,Malinda.C.Young,Steven.L.Regen.Detection of Nonideal Mixing of Phospholipids in Fluid Bilayers[J].Am.Chem.Soc,2000,122:1200-1204.
[38]H.T.Tien,Zdzislaw Salamon.Cyclic voltammetry studies of biomembranes deposited onplatinum by self assembly[J].B ioelectrochemestry and Bioenergetics,1989,22:211-218.
[39]刁鹏,姜殿禄,崔晓莉,顾登平,童汝亭.一种制备铂支撑自组装双层类脂膜新方法[J].电化学,1999,5(3):288-293.
[40]王建国,江黎丽,惠飞,杨薇薇,吕慧,孙巧花.脱氧胆酸钠与支撑磷脂双层膜作用的电化学研究[J].化学学报,2007,65(3):239-245.
[41]王建国,滕人瑞,汪尔康.杂多酸K_7Fe_3 P_2W_(17)O_(62)H_2对硫醇一磷脂杂化双层膜通透性的影响[J].化学学报,2004,59(12):2138-2142.
[42]马勇,霍俊杰,惠飞,王建国,韩正波,臧树良.Keggin型杂多酸H3 PMo_(12)O_4对磷脂双层膜电化学行为的影响[J].辽宁大学学报,2006,33(2):97-100
[43]刘妍,陈艳艳,靳刚.硅基片上的自组装双层磷脂分子膜层[J].纳米器件与技术.2007,4(1):22-26
[44]Yan Li Zhang,James Dunlop,Thai Phung,Angelica Ottova,H.T.Tien.Supported bilayerlipid membranes modified with a phosphate ionophore[J].ELSEVEIR,2006,21:2311-2314
[45]Yu-Feng Zhang,Xin-Hou,Gang Wu,Rong-Chang Li,Xin-Wen Qiao,H.Ti Tien.Study onselectivity of permeating chiral complexes in bilayer lipid membranes(BLM)[J].ELSEVEIR,1999,1:238-241.
[46]T.Hianik,J.Dlugopolsky,M.Gyeppessova,B.Sivak,H.T.Tien,A.Ottova-Leitmannova.Stabilization of bilayer lipid membranes on solid supports by trehalose[J].ELSEVEIR,1996,39:299-302.
[47]A.Tripathy,H.T.Tien,Angelica L.Ottova.A study of reconstituted anion charmels usinglipid bilayers[J].ELSEVEIR,1998,44:183-199.
[48]Li Wang,Xin-Pu Hou,Angelica Ottova,H.T.Tien.Receptor-ligand interactions in areconstituted bilayer lipid membrane[J].ELSEVEIR,2000,2:287-289.
[49]赵艳.方炎.双层类脂膜成膜过程的电化学方法研究[J].电化学,2004,10(1):70-74.
[50]陈华丽,韦云隆,刘盛平.碘修饰的S-BLM生物传感器研究[J].汕头大学学报,2003,18(1):19-23
[51]高宏,罗国安.双层磷脂膜的电化学性质及其在生物传感器中的应用[J].分析科学学报.2002,18(1):70-74.
[52]Jianguo Wang,Li Wang,Shaoqin Liu,Xiaojun Han,Weimin Huang,Erkang Wang.Interaction of K Fe3qP W O H with supported bilayer lipid[J].ELSEVEIR,2003,106:31-38
[53]韩晓军,宋永海,昊正岩,张柏林,汪尔康.钙离子对支撑磷脂膜离子通道行为的诱导作用[J].高等学校化学学报.2001,22(3):12 1298-1300.
[54]Kinji Asaka,H.T.Tien,Angelica Ottova.Voltammetric study of charge transfer acrosssupported bilayer lipid membranes(s-BLM)[J].ELSEVEIR,1999,40:27-37.
[55]蔡红,王斌,张占军,蔡生民.不锈钢支撑双层类脂膜离子传感器的电化研究与应用. 应用化学[J].2003,20(4):307-311.
铩颷56]蔡红,王斌,张占军.C_(60)修饰的s-BLM离子传感器的研究与应用[J].安徽大学学报,2003,27(1):84-88.
[57]Kinji Asakaa,Angelica Ottovab,H.T.Tien.Mediated electron transfer across supportedbilayer lipid membrane(s-BLM)[J].ELSEVEIR,1999,354:201-207.
[58]H.T.Tien,Lei-Guang Wang,Xing Wang,Angelica L.Ottova.Electronic processes insupported bilayer lipid membranes(s-BLM)containing a geodesic form of carbon(fullerene C60)[J].ELSEVEIR,1997,43:161-167.
[59]程洪艳,胡颖,王燕平,方炎.C_(60)衍生物修饰的固体支撑双分子层磷脂膜(s-BLM)分子器件的电化学和拉曼光谱研究[J].光谱学与光谱分析.2002 22(3):403-406.
[60]Jian-Shan Yea,Angelica Ottovab,H.T.Tien,Fwu-Shan Sheu.Nanostructured platinum-lipidbilayer composite as biosensor[J].ELSEVEIR,2003,59:65-72.
[61]H.T.Tien,Samuel H.Wurster,Angelica L.Ottova.Electrochemistry of supported bilayerlipid membranes:background and techniques for biosensor development[J].ELSEVEIR,1997,42:77-94.
[62]J.Sabo,A.Ottova,G.Laputkova,M.Legin,L.Vojcikova,H.T.Tien.A combined AC-DCmethod for investigating supported bilayer lipid membranes[J].ELSEVEIR,1997,306:112-118.
[63]扈显琦,梁成浩.交流阻抗技术的发展与应用[J].腐蚀与防护,2004,25(2):57-60
[64]程志亮,杨秀荣.电化学交流阻抗技术表征自组装多层膜[J].分析化学,2001,29(1):6-10.
[65]高宏,罗国安,冯军.硫醇.磷脂混合双层膜的电化学性质及其与蜂毒素的相互作用研究[J].化学学报,2001.59(2):220-223.
[66]欧阳钟灿,刘寄星.从肥皂泡到液晶生物膜[M].长沙:湖南教育出版社,1995.
[67]崔大付,张兆田,熊小芸,徐建华.生物电子学的研究与发展[J].中国科学基金,2004,4:205-211.
[68]崔生辉,李景云,马越.细菌对氟喹诺酮类药物的耐药机制[J].中国药房,2007,18(14).
[69]赵艳,方炎.BLM成膜液中胆固醇与卵磷脂相互作用的光谱学研究[J].光散射学报,2004,16(1):79-83
[70]Milhaud J,Ponsinet V,Takashi M,Michels B.Interactions of the drug amphotericin B withphospholipid membranescontaining or not ergosterol:new insight into the role of ergosterol[J].Biochimica et Biophysica Acta,2002,95:1558
[71]杨运煌.血清中分子间相互作用的NMR研究[D].中国科学院武汉物理与数学研究所.2004
[72]张晋蓉,林财珠,杨锡馨,吕凯荣,盛国庆,戴体俊.异丙酚对PC12细胞和脂质体膜流动性的影响[J].中国临床药理学与治疗学.2003 8(2):129-132.
[73]盛国庆,张晋蓉,戴体俊,蒲小平,李长龄.异丙酚对PC12细胞膜流动性及[Ca~(2+)]的影响[J].中国药理学通报,2002,18(3):264-266.
[74]张德林.茶多酚产品的主要成分及抗油脂氧化机理的研究报告[J].广州食品工业科技,1993,3:27-31.
铩颷75]宋玉光,孙健,Nohl Hans,刘扬.几种含羟基化合物对红细胞膜流动性的影响[J].波谱学杂志.2005,22(4):351-355.
[76]谢祖芳,夏金虹,晏全.聚酰胺吸附硝基苯酚的热力学与机理探讨[J].化工技术与开发,2003,32(2):10-13.