硒化聚甘露糖醛酸的合成及抗阿尔茨海默症细胞氧化与凋亡  

Seleno-polymannuronate Synthesis and Resistance to Oxidation and Apoptosis in Alzheimer's Disease Cells

作　　者：朱志杰[1] 刘琼[1] 陈平[1] 续旭[1] 倪嘉缵[1] 杨思林 宋云 

机构地区：[1]深圳大学生命科学学院,深圳518060 [2]华信生物药业股份有限公司,界首236500

出　　处：《高等学校化学学报》2013年第1期115-122,共8页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:31070731;31000770);广东省自然科学基金(批准号:10151806001000023);深圳市科技研发项目(批准号:CXB201005240008A)资助

摘　　要：以聚甘露糖醛酸为原料,采用先磺化、再硒化的方法合成了硒化聚甘露糖醛酸,产率为54%,产物硒含量为437.25μg/g.在2.5μmol/L硒浓度下,硒化聚甘露糖醛酸促细胞生长能力达到最适范围,能保护细胞免受过氧化氢损伤,显著提高阿尔茨海默症(AD)模型细胞N2a-APP695-sw中的超氧化物歧化酶和谷胱甘肽过氧化物酶的活性,降低细胞内活性氧自由基,增加线粒体膜电位,抑制细胞色素C的释放,在促进Bcl-2表达的同时抑制Bax的表达,从而具有抑制AD细胞凋亡的功能.硒化聚甘露糖醛酸也能抑制AD病理相关蛋白BACE1和APP的表达.结果表明,硒化聚甘露糖醛酸在抗AD方面具有潜在的应用前景.Selenium deficiency is closely relate to multiple diseases. Supplementation with adequate amount of selenium is very important for human health. As various selenium compounds have different biological effects, preparation and functional study of new product are essential for the discovery of selenium-containing drug. In this work, polymannuronate（PM） was used as the raw material to synthesize sulfonated polymannur- onate （S-PM）. Seleno-polymannuronate （Se-PM） was then prepared by the replacement of sulfonated group in S-PM with sodium selenite. The yield of Se-PM synthesis was 54% with a selenium content of 437.25 μg/g. Purified Se-PM was used to study its antioxidative property and effect on Alzheimer＇ s disease （AD）, using N2a-APP695-sw cells as an AD model. Cell viability was detected by CCK-8 assay. Intracellular reactive oxy- gen species（ROS） was measured by flow cytometry. Mitochondrial membrane potential and cytochrome C re- lease were detected by laser scanning confocal microscope. The expression levels of cell apoptosis and AD pa- thology relevant proteins were analyzed by Western Blot. The results showed that the optimum selenium con- centration was 2. 5 μmol/L for prevent cells from the oxidative Se-PM to significantly damage of hydrogen increase cell viability. Se-PM at this concentration could peroxide, inhibit intracellular ROS, increase the activity of superoxide dismutase and glutathione peroxidase, promote mitochondrial membrane potential, and suppress cytochrome C release into cytoplasm. Meanwhile, Se-PM could also increase Bel-2 expression and decrease Bax expression, inhibit the expression of AD pathology relevant proteins BACE1 and APP. Those results indi- cated that Se-PM could resist AD through the prevention of cell apoptosis and amyloid plaque formation, a key pathological feature of AD. It also provides basic data for the development of new anti-AD drug.

关 键 词：甘露糖醛酸 硒化聚甘露糖醛酸 阿尔茨海默症(AD) 活性氧自由基(ROS) 细胞凋亡 

分 类 号：O629[理学—有机化学] O613.52[理学—化学]