反相微乳体系棕色色素胆结石的体外模拟

【作者】 张雪茹；

【导师】 张胜义； 沈玉华；

【作者基本信息】 安徽大学 ， 无机化学， 2002， 硕士

【摘要】 本文用TX-100(聚乙二醇辛基苯基醚——简称乳化剂OP／正己醇／环己烷／水按比例组成)反相微乳体系对棕色色素型胆结石的主要成分进行了仿生模拟，考察在接近人体环境中棕色色素型胆结石的形成机理，对棕色色素型胆结石的治疗和预防具有重要意义。 本文使用反相微乳体系合成了胆红素钙，(并在水模拟环境中合成胆红素钙做对比)和胆红素钙-氨基酸复合粒子，并考察了同时存在其它金属离子和含氧酸盐时对胆红素和钙离子配位的影响，对碳酸钙，还研究了氨基酸也同时存在时对胆红素钙沉淀的影响。对所合成的粒子进行了中、远红外分析，考察配合物中胆红素和钙离子的配位情况；用EDTA溶解后，做紫外可见光谱定量分析，研究所合成的粒子中胆红素钙的可溶解性。用X射线衍射分析考察了胆红素钙在生物模拟体系和胆红素钙-氨基酸复合粒子等物质的晶体结构；并使用透射电镜分析，观察了粒子的形貌；用ICP-AES法测定胆红素配合物中金属离子含量。此外，还用Zeta电位分析测试了胆红素钙和胆红素钙-氨基酸粒子的稳定性。 研究表明，在生物模拟体系合成的胆红素钙具有非化学计量比的性质，胆红素和钙离子配位情况与有机溶剂体系、LB膜体系及固相研磨体系中胆红素和钙离子的配位情况不同，特别是反相微乳体系中合成的胆红素钙具有膜控晶体生长特性。反相微乳体系中胆红素钙的钙离子的含量比水模拟体系相同反应比时得到的胆红素钙的钙离子含量偏低。反相微乳体系所合成的胆红素钙为球形纳米级粒子，在酸性条件下容易凝聚。 氨基酸可以和胆红素钙发生较强的相互作用。各种氨基酸对胆红素钙的溶解都有抑制作用。由于氨基酸对胆红素和钙离子之间的配位有影响，溶解得到的胆红素的微结构发生变化。根据对胆红素钙-色氨酸和胆红素钙-酪氨酸的X射线分析，色氨酸和酪氨酸的晶体结构和胆红素钙存在差异。胆红素钙-氨基酸的复合粒子的形貌和胆红素钙不同。加入氨基酸后，复合粒子更容易凝聚。 加入其它金属离子后对胆红素钙的研究表明：镁离子对钙离子存在促进作 ＿女敞人学仙什毕业论义 嫡匹－＿用，生成胆红素难溶状的可能性增加。鳃离子对胆红素和钙离子的结合凤有促进 作用。铜离子可以和胆红素发上氧化还原反应，在含量较少时促进胆红素和钙离＿子的结合。铁离子、锰离子和钙离子之间的竞争作用较明显。铝离子对胆红素和．’钙离子之问的结合作用较小。钡离子对胆红素和钙离子的结合有抑制作用。 I－ Z 碳酸钙、磷酸钙、胆酸钙等难溶盐和胆红素钙混合在一起，使胆红素和钙 离子的结合变得松散相对来说较容易溶解。但胆汁酸盐对胆红素钙的作用较复 ＿“杂，与胆汁酸盐的存在形式有关。复合体系中存在氨基酸时，对胆红素钙的溶解－同样存在抑制作用，但作用不明显。另外，胆汁酸盐对胆红素和钙离子的结合影 响较大。胆酸盐含量较高时，胆红素钙骨架发生改变。 。总体来说，棕色色素型胆结石的形成是一复杂过程，是生物大分子参与下＿的异相形核过程。各种因素对胆红素和钙离子的结合都有影响。更多还原

【Abstract】 In this paPer, the basic constitutes of pigment gallstone were synthesized inbiomimetic system. This study has discussed the pathogenesis of pigmnt gallstone.A series of calcium bilirubinates, calcium bilirubinate-amino acid complexeswere synthesised in reverse microemulsion. Meanwhile, a series of calciumbilirubinate were synthesized in water to contrast. The actions of other metal ions’calcdri carbonate’ calcium phosPhate and cholic acid with calciurn bilirubinate inreverse microemulsion were discussed in this paper too. The particles werecliaracterized by Fourier transform infrared, powder X-ray diffrachon, Uv-vis sPectra,induchvely couPled plasma atomic emission sPectrometry, transmission electronmicroscoPic and Zetasirer.The results showed that calcium bilinmate synthesired in biodsetic systemwere non-stoichiometrical. Bilboin and calcium had sPecial coordination states inthis system. The coordination states were different to calcium bilboinate synthesizedin organic solvent, LB system and so on. Most of calcinm bilirubinates hadevident oriental groWth, and there were controlled crystal growth in reversemicroemulsion. The contents of ca1cium of calcium bilirubinate synthesized inreversed microemulsion were less than the contCnts of calcium of calcium bilAnbinatesynthesized in water. Calcium bilirubinate synthesised in reverse microemulsion werespheric particles about 80nm. They had narrow size distribution and were easily toagglomerate in acid conditionThe actions of amino acid with calcium bilinJbinate were discussed in this paper.Anino acid restrained the solubility of calcium bilinJbinate, and themicroconfiguration of bilirubin had changed. The aPpearances of calciumbilirubinate-amino acid were different from calcium bilirubinate. Ca1cium bilirubinate--amino acid complexes were morc easily to agglomerate than calcium bilirubinate.Magncsium ion and strontium ion facilitated the combination of biIirubin withcalcium. Coppcr had redox acti()n with bilirubin, when the contcnt of copper was3k’k{;liat If t8all&x Mwlittle, this ion facilitated the combination of bilirubin with calcium. Iron ion andmanganese ion competed with calcium ion. Barium ion restrained the combination ofbilirubin with calcium. Aluminum ion had little action with the combination ofbilirubin with calcium.Calcium carbonatC, calcium phosPhate and cholic acid accelerated the solutionof calciurn bilirubinate.In conclusinn, the process of form pigInent gallstone was intricate, biomolecularpAncipated in this process, and every e1ement will infect the fOrm of pwientgallstone.更多还原