Inhibition Of HIAPP Aggregation In Type Ⅱ Diabetes By Functional Graphene Oxide And Defect Mesoporous Silica

Type 2 diabetes mellitus(T2DM) is a kind of endocrine disease, which is folded into amyloid protein. A large number of studies show that the main component of this protein precipitation is human islet amyloid protein(h IAPP). h IAPP misfolded formation oligomers and mature fibrils process accompanied apoptosis, and apoptosis may be due to caused by oxidative stress, mitochondrial damage or cell membrane permeability changes. To prevent the formation of toxic h IAPP fibrils is a reasonable way to treat type 2 diabetes mellitus.According to pathogenesis of type 2 diabetes mellitus, in this paper, we designed and synthesized a new kind of n GO@PEG@E nanocomposite and another kind of defect luminescent mesoporous silica supported h IAPP partial fragment methyl nanoparticles. The effects of these two kinds of nanoparticles on the inhibition of hIAPP induced aggregation and neurotoxicity were systematically studied, and the mechanism of inhibiting the aggregation of h IAPP were also discussed.This paper is divided into three chapters:The first chapter: This paper briefly introduces the type 2 diabetes mellitus, its pathogenesis, the role of h IAPP in the pathogenesis and the mechanism of h IAPP aggregation. Then, the research progress of various drugs and nano materials in hIAPP aggregation is reviewed. Finally, the significance and purpose of this topic are discussed.In the second chapter, we designed and synthesized nano composite(nGO@PEG@E) using PEG and insulin derivatives as EALYLV modified graphene oxide. Nano graphene oxide(n GO) can adsorb hIAPP monomer, which can reduce the concentration of free h IAPP in solution to achieve the purpose of inhibiting the aggregation of fiber. EALYLV is insulin derivatives, it is possible to specific combination of hIAPP, can form a strong salt bridge with arg11 hIAPP side chain, it is also able to from the arg11 across to hIAPP residues Phe15 blocking molecules to form fibres of main function region, thereby inhibiting the accumulation of hIAPP. nGO@PEG@E nanoparticles could not only inhibit the aggregation of h IAPP, but also protect the INS-1 cells from the toxicity of h IAPP, stabilize the membrane potential and reduce the intracellular reactive oxygen species.In the third chapter, hIAPP is a 37 amino acid polypeptide, fragment 8-20,20-29 and 30-37 have the ability to form a fiber. NFGAIL acts as a short hIAPP amyloid aggregation nucleus, which has the ability to selfassemble into a beta folding structure and a cytotoxic fiber. GA(NFN-Me) IL(N-Me) can specifically bind and inhibit the aggregation of h IAPP. Defect mesoporous silica(DLMSNs) can be more conducive to the study of cell absorption. In this paper, we synthesized modified chitosan and load the N-Me) Ga(N-Me) il DLMSNs DL@CS@NF, it can inhibit hIAPP aggregation, TEM and AFM experiments in obvious can see after DL@CS@NF after treatment with hIAPP almost can not see mature fiber. In the experimental cell DL@CS@NF can reduce cytotoxicity and active oxygen protective cells. The nanoparticles we combined can serve as potential drugs for the treatment of type 2 diabetes mellitus.