【作者】 李宪璀；

【导师】 范晓；

【作者基本信息】 中国科学院海洋研究所 ， 海洋生物， 2001， 博士

【摘要】 以α-葡萄糖苷酶抑制剂筛选模型为基础，以大型海藻为研究对象，旨在发现海藻中能够预防与治疗糖尿病以及抗艾滋病的活性物质。在对青岛沿海海藻脂溶性提取物进行了普筛的基础上，以石莼为原料追踪并分离鉴定出了酶活性抑制剂SQ0；建立了快速准确测定海藻中SQG的方法，并测定了一些大型藻中SQG的含量及季节变化，为选择提取SQG的原料提供了依据；建立了大量制备SQG的方法，为深入研究SQG的活性机理和SQG进入动物试验阶段进行基础研究工作；研究并提出了SQG的酶抑制活性机理，为进行药理研究提供理论依据。 本文的工作由六部分组成，研究内容介绍如下：1、采用α-葡萄糖苷酶抑制剂筛选模型对青岛沿海二十种海藻的脂溶性提取物进行了初步的活性筛选；初筛结果表明，海藻中普遍含有能够抑制α-葡萄糖苷酶活性的活性物质；2、对石莼中的活性组份进行了追踪并鉴定出了酶抑制活性物质1，2-二酚基-3-（6-脱氧-6-磺酸基-α-D-吡喃型葡萄糖苷基）-sn-甘油脂（SQG）。3、建立了快速准确直接测定SQG含量的方法。通过研究表明azure A比色法灵敏度高，检测限低（0.00442μmol），线性范围宽（0.00442-0.11488μmol），重现性好。4、测定了二十二种海藻中SQG的含量以及部分海藻SQG含量的季节变化，发现石莼中SQG含量较高并且受季节影响少。5、以石莼为原料建立了规模制备SQG的方法，为进一步研究SQG的生物活性奠定了基础。6、通过对SQG的酶抑制活性研究，首次测得SQG的IC₅₀为20μM。不同SQG浓度下酶动力学研究结果表明SQG对α-葡萄糖苷酶的抑制属于非竞争性抑制，抑制常数K_i为72.31μM;研究了SQG的构效关系并提出了SQG的酶抑制活性机理。更多还原

【Abstract】 The aim of this research is to find anti-diabetes and anti-HIV substances from macroalgae with cL-glucosidase as target. The large-scale screening of a-glucosidase inhibitor from the organic solvent extracts of algae collected from Qingdao was completed, and then the cx-glucosidase inhibitor SQG was isolated and identified after screening of inhibitor from U/va lacuca L.. A rapid spectrophotometric method for determination of SQG was established, and the content and the change with season of SQG in algae were investigated for the selection of material. The method of large-scale preparation of SQG was established to facilitate the discovery of its inhibition mechanism and preclinical investigation. The inhibition theory of SQG on the a-glucosidase was postulated, and it is helpful for further research on drug. This dissertation consists of six sections, and the contents are as the follows. 1. Screening of c-glucosidase inhibitor from the organic solvent extracts of 20 species of alga was completed, and the result indicated that most of alga contains the inhibitor against i-glucosidase 2. The cL-glucosidase inhibitor SQG was isolated and identified after screening from U/va lctciucct L.. 3 A rapid spectrophotometric method for determination of SQG was established. This method has low limit (0.00442imol). 4.. The content and the change with season of SQG in algae were investigated, and we find U/va /actuca L contained large amount of SQG and the content in this species is relatively stable. 5. A method for large-scale preparation of SQG from U/va /actuca L. was described. 6. The 1C50 of SQG was 201.tM and the result of enzyme kinetics show that SQG is the lion-competition inhibitor, and the inhibition constant Ki is 72.31 iM; The function and structLlre of SQG was investigated and the inhibition mechanism was put forward.更多还原