乙醛诱导的神经细胞毒性机制及虾青素的保护作用

发布时间：2018-04-04 23:14

本文选题：乙醛　切入点：虾青素　出处：《哈尔滨工业大学》2013年硕士论文

【摘要】：本课题以人神经母细胞瘤系SH-SY5Y为模型，研究乙醇在体内的重要代谢产物乙醛对神经细胞的损伤作用及其分子机理，以及抗氧化剂虾青素对乙醛诱导的神经毒性的抑制作用。研究发现，当SH-SY5Y细胞以不同浓度乙醛处理24h后，，细胞的生存率随着乙醛浓度的升高而下降，而作为凋亡指标的caspase-3蛋白酶活却呈现上升趋势，细胞内发生明显凋亡现象。细胞凋亡抑制蛋白Bcl-2、Bcl-xl和凋亡促进蛋白Bax的比例Bcl-2/Bax、Bcl-xl/Bax随乙醛浓度上升而下降，细胞通过线粒体凋亡途径引发的凋亡现象越来越明显。作为细胞氧化应激水平指标的丙二醛（Malondialdehyde，MDA）含量也随乙醛浓度上升呈现上升趋势，说明细胞内的氧化应激水平逐步增强。虾青素预处理则对乙醛诱导的细胞毒性具有抑制作用，使细胞的生存活性明显上升，caspase-3蛋白酶活显著下降，并抑制乙醛诱导的Bcl-2/Bax、Bcl-xl/Bax下降，并且虾青素预处理明显降低氧化应激水平。因此，乙醛可能通过升高细胞内氧化应激水平、升高凋亡促进蛋白表达及下调凋亡抑制蛋白表达诱导SH-SY5Y细胞凋亡并降低其生存活性。而虾青素则通过降低乙醛诱导的氧化应激和抑制乙醛对凋亡途径关键蛋白表达的影响降低乙醛诱导的细胞凋亡，提高细胞的生存活性。
[Abstract]:Using human neuroblastoma cell line SH-SY5Y as a model, this study was designed to study the damage and molecular mechanism of acetaldehyde, an important metabolite of ethanol in vivo, and the inhibitory effect of astaxanthin on neurotoxicity induced by acetaldehyde.It was found that when SH-SY5Y cells were treated with different concentrations of acetaldehyde for 24 hours, the survival rate of SH-SY5Y cells decreased with the increase of acetaldehyde concentration, while the activity of caspase-3 protease, as an index of apoptosis, increased, and apoptosis occurred in the cells.The ratio of apoptosis inhibitor Bcl-2Bcl-xl and apoptosis-promoting protein Bax decreased with the increase of acetaldehyde concentration, and the apoptosis induced by mitochondrial apoptosis was more and more obvious.The content of malondialdehyde (MDA) Malondialdehyde (MDAs), which is the index of cellular oxidative stress level, also increased with the increase of acetaldehyde concentration, indicating that the level of intracellular oxidative stress increased gradually.Astaxanthin pretreatment inhibited the cytotoxicity induced by acetaldehyde, significantly increased cell viability and decreased the activity of caspase-3 protease, and inhibited the decrease of Bcl-2 / Bax-xl / Bax induced by acetaldehyde. Astaxanthin pretreatment significantly decreased the level of oxidative stress.Therefore, acetaldehyde may induce apoptosis and decrease the survival activity of SH-SY5Y cells by increasing the level of oxidative stress, increasing the expression of apoptosis-promoting protein and down-regulating the expression of apoptosis-inhibiting protein.Astaxanthin reduced the oxidative stress induced by acetaldehyde and inhibited the expression of acetaldehyde on the key protein of apoptosis pathway. It decreased the apoptosis induced by acetaldehyde and improved the viability of cells.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R114

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