两种多吡啶钌异构体用于抑制Aβ42纤维化和降低Aβ42细胞毒性的研究  

The Study of Two Isomers of Ruthenium Polypyridyl Complexes on Inhibiting Aβ42 Fibrillization and Reducing the Cytotoxicity of Aβ42

作　　者：王彤 李贞华 张园芳 王祎 张黔玲 师红东 WANG Tong;LI Zhenhua;ZHANG Yuanfang(The 964 th Hospital of the Joint Logistic Support Force of the Chinese People’s Liberation Army,Changchun 134000,China)

机构地区：[1]中国人民解放军联勤保障部队第九六四医院神经内科,吉林长春134000 [2]深圳大学化学与环境工程学院,广东深圳518071

出　　处：《中风与神经疾病杂志》2019年第9期772-777,共6页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金面上项目(No.21671137)

摘　　要：目的研究了两种含羟基多吡啶钌配合物Ru[(phen)2(DHOPIP)]2+(p23OH)和Ru[(phen)2(DHMPIP)]2+(p25OH)对Aβ42纤维化的抑制。方法通过ThT荧光实验、TEM和AFM形貌表征、BCA可溶性蛋白含量测定、Aβ内源性荧光滴定及MTT细胞活性实验系统研究了钌配合物对Aβ42聚集的影响。结果TEM和AFM结果表明,在钌配合物的存在下,Aβ42不形成纤维体,而是以细小的颗粒存在。荧光滴定实验结果表明两种钌配合物均能显著地淬灭Aβ42的内源性荧光。最初,钌配合物对Aβ42的荧光淬灭以静态荧光淬灭为主,随着钌配合物浓度的增加,钌配合物对Aβ42的荧光淬灭逐渐转变为动态荧光淬灭;钌配合物与Aβ42之间主要通过静电和疏水作用,其表观结合常数较小;细胞毒性研究表明两种钌配合物均有较低的细胞毒性,并能降低细胞内由于Aβ42聚集所引起的细胞毒性。结论两种钌配合物均能有效地抑制Aβ42纤维化,并表现出明显的剂量相关性;在相同条件下,p23OH的抑制效果优于p25OH。Objective[Ru(phen)2(DHOPIP)]2+(p23OH)and[Ru(phen)2(DHMPIP)]2+(p25OH)with dihydroxy were used to studied their inhibitory effect on Aβ42 fibrillization.Methods The inhibitory effect on Aβ42 fibrillization of the two ruthenium complexes were characterized by ThT fluorescence assay,AFM,TEM,fluorescence titration,the measurement of soluble protein content and MTT assay.Results TEM and AFM results showed that there was small amounts of amorphous Aβ42 aggregation rather than fibers when Aβ42 treated with ruthenium complexes.The results of fluorescence titration showed that the fluorescence of Aβ42 was mainly quenched by static fluorescence quenching and the effect of dynamic quenching was enhanced with the increase of the amount of ruthenium complexes.The apparent binding constants of the two ruthenium complexes with Aβ42 were less than 0.08 mol/L,which indicated that the interaction between the complexes and Aβ42 was weak and it was mainly showed in the form of non-covalent interactions,such as electrostatic interaction,and hydrophobic.In addition,the ruthenium complexes showed low cytotoxicity on cells.Moreover,they could decrease the cytotoxicity of Aβ42 aggregation with hypo-toxic could decrease the cytotoxicity caused by Aβ42.Conclusions The p23OH and p25OH could effectively inhibit aggregation of Aβ42,and the inhibitory effect of p23OH was better than that of p25OH.

关 键 词：阿尔茨海默病 Β-淀粉样肽 多吡啶钌配合物 Aβ42纤维化 Aβ抑制剂 

分 类 号：R749.1+6[医药卫生—神经病学与精神病学] R34[医药卫生—临床医学]