【作者】 王静；

【导师】 周星飞；

【作者基本信息】 宁波大学 ， 物理学， 2023， 硕士

【摘要】 淀粉样蛋白的聚集与许多疾病有着密切相关。其中一种主流观点认为多肽聚集时产生的活性氧(ROS)可能会影响神经细胞的结构和功能,进而导致此类疾病。虽然目前使用的抗氧剂清除ROS的效果很好,但是大量的摄入这些抗氧化剂会对人体产生一些严重的危害。已有实验证明注射氢水对阿尔茨海默症的小鼠有明显的治疗效果。但目前所面临的问题是氢气能够缓解症状的微观机理还不是很清楚,本课题的主要研究内容是氢气是否能够作为抗氧化剂,对不同淀粉样多肽聚集产生的ROS起到清除作用,以达到缓解病症的效果。本文第一部分工作以人胰岛淀粉样蛋白h IAPP(11-28)为主要研究对象,探究铜离子与h IAPP(11-28)的结合,发现铜离子能够导致h IAPP(11-28)的寡聚化,并且能够促进h IAPP(11-28)聚集产生ROS。在此基础上继续研究了氢气对h IAPP(11-28)聚集产生ROS的影响。Amplex Red荧光法和电子顺磁共振波谱仪(EPR)测量数据表明氢气均能显著中和多肽聚集过程中产生的ROS,说明氢气具有良好的抗氧化作用。进一步探究氢气抗氧化效果,本文第二部分工作以β-淀粉样蛋白Aβ(1-16)为主要研究对象,在铜离子与Aβ(1-16)混合溶液中通入足量氢气,Amplex Red荧光法和EPR测量数据表明氢气均能显著中和铜离子与Aβ(1-16)集过程中产生的ROS,进一步说明氢气具有良好的抗氧化作用。为了探究氢气的抗氧化作用是否具有普适性,本文第三部分工作在合成的FFH短肽溶液中通入足量分子态的氢气,Amplex Red荧光法和EPR测量数据表明氢气均能显著中和铜离子与FFH短肽集过程中产生的ROS,说明氢气具有良好的抗氧化作用,且具有一定的普适性。此外,我们还对氢气和ROS的相互作用机理也做了简要分析。更多还原

【Abstract】 The aggregation of amyloid polypeptides is closely related to many diseases.One mainstream view is that reactive oxygen species(ROS)generated by peptide aggregation may affect the structure and function of nerve cells,thus leading to such diseases.Although the currently used antioxidants have a good effect of scavenging ROS,a large amount of intake of these antioxidants will cause some serious harm to human body.However,experiments have proved that hydrogen water injection has obvious therapeutic effect on Alzheimer’s disease mice.However,the current problem is that the microscopic mechanism by which hydrogen can alleviate symptoms is not very clear.The main research content of this topic is whether hydrogen can act as an antioxidant to scavenge ROS generated by the aggregation of different amyloid polypeptides,so as to achieve the effect of alleviating disease.The first part of this thesis focuses on human pancreatic amyloid h IAPP(11-28),explores the binding of copper ions with h IAPP(11-28),and finds that copper ions can cause the oligomerization of h IAPP(11-28),and promote the aggregation of h IAPP(11-28)to produce ROS.On this basis,the effect of hydrogen on the production of ROS by h IAPP(11-28)aggregation was further studied.The results of Amplex Red fluorescence analyzer and electron paramagnetic resonance spectroscopy(EPR)showed that hydrogen could significantly neutralize ROS produced in the process of polypeptide aggregation,indicating that hydrogen had a good antioxidant effect.To further explore the antioxidant effect of hydrogen,the second part of this thesis takesβ-amyloid Aβ(1-16)as the main object of study.Sufficient hydrogen is injected into the mixed solution of copper ion and Aβ(1-16).The results of Amplex Red fluorescence analyzer and EPR showed that hydrogen could significantly neutralize ROS produced in the process of copper ion and Aβ(1-16)aggregation,which further indicated that hydrogen has a good antioxidant effect.In order to explore whether the antioxidant effect of hydrogen is universal,in the third part of this thesis,sufficient molecular hydrogen was injected into the synthetic FFH short peptide solution.The measured data of Amplex Red fluorescence analyzer and EPR showed that hydrogen could significantly neutralize ROS produced in the process of copper ion and FFH short peptide set.It shows that hydrogen has good oxidation resistance and has certain universality.In addition,we also briefly analyzed the interaction mechanism between hydrogen and ROS.更多还原