中文摘要：

目的探讨二肽基肽酶-4抑制剂（DDP-4I）对阿尔茨海默病（AD）样神经退行性改变的保护作用及其机制。方法取对数生长期的人神经母细胞瘤细胞SH-SY5Y分为6组：空白对照组（CON组），含1‰二甲基亚砜（DMSO）的磷酸盐缓冲液（PBS）处理12h；wortmannin干预组（W组），0.03μmol/Lwortmannin处理12h；DPP-4I干预组（DPP-4I组），10μmol/LDPP-4I处理12h；DPP-4I与wortmannin共同干预组（DPP-4I+W组），10μmol/LDPP-4I预处理2h，再给予0.03μmol/Lwortmannin处理12h；DPP-4I+wortmannin+Ex9-39共同干预组（DPP-4I+W+Ex9-39组），10μmol/LEx9-39预处理2h，再加入10μmol/LDPP-4I作用2h，最后0.03μmol/Lwortmannin处理12h；Ex9-39干预组（Ex9-39组），10μmol/LEx9-39处理12h。MTT法检测各组细胞活性的变化，Westernblot法检测各组微管相关的tau总蛋白（tau-5）及其不同磷酸化位点（pSpS199/202、pT231和pS396）、神经丝（NFs）相关蛋白（NF-H、NF-M）以及胰岛素信号通路PI3K/Akt/GSK-3β中关键酶的磷酸化水平。结果（1）与CON组相比，W组细胞活力下降，pSpS199/202、pT231、pS396以及NF-H/M的磷酸化水平升高，而DPP-4I组细胞活力上升，上述指标的磷酸化水平下降；与W组相比，W+DPP-4I组的细胞活力上升，上述指标的磷酸化水平下降。（2）与CON组相比，Ex9-39组细胞活力下降，pSpS199/202、pT231、pS396以及NF-H/M的磷酸化水平升高；与DPP-4I+W组相比，DPP-4I+W+Ex9-39组上述指标发生相同的变化。（3）与CON组相比，W组p-PI3K、p-Akt、p-GSK3β水平下降，DPP-4I组p-PI3K、p-Akt、p-GSK3β水平上升；与W组相比，DPP-4I+W组p-PI3K、p-Akt、p-GSK3β水平上升。结论DPP-4I可通过提高GLP-1的浓度和激活PI3K/Akt/GSK-3β信号通路来改善wotmannin诱导的AD样的tau蛋白和神经丝的过度磷酸化，保护神经细胞的退行性变。

英文摘要：

Objective To explore the protective effects of dipeptidyl peptidase-4inhibitor(DPP-4I)on AD-like neurodegenerative changes and its mechanism.Methods The human neuroblastoma cell line SH-SY5Y on the logarithmic phase was divided into six groups:control group(CON group,treated with PBS contained1‰DMSO for12h),wortmannin intervention group(W group,treated with0.03μmol/L wortmannin for12h),DPP-4I intervention group(DPP-4I group,treated with10μmol/L DPP-4I for12h),both DPP-4I and wortmannin intervention group(DPP-4I+W group,pre-treated with10μmol/L DPP-4I for2h,then0.03μmol/L wortmannin for12h),DPP-4I,wortmannin and Ex9-39intervention group(DPP-4I+W+Ex9-39group,pre-treated with10μmol/L Ex9-39for2h,then10μmol/L DPP-4I for2h followed by0.03μmol/L wortmannin for12h),and Ex9-39intervention group(Ex9-39group,treated with10μmol/L Ex9-39for12h).MTT assay was used to detect the cell vitality.Western blot assay was used to detect the level of total tau protein(tau-5)andphosphorylated tau at different sites(pSpS199/202,pT231and pS396),the level of phosphorylated neurofilaments(NF-H,NF-M)and phosphorylation of critical enzyme in PI3K/Akt/GSK-3βsignaling pathway.Results(1)The cell vitalitydecreased,the levels of pSpS199/202,pT231,pS396and NF-H/M increased significantly in W group than those in CONgroup.However,comparing with CON group,the above mentioned parameters reversed in DPP-4I group.Comparing with Wgroup,the cell vitality increased and phosphorylated levels of above mentioned indices were decreased in DPP-4I+W group.(2)The cell vitality showed a decline trend while the levels of phosphorylation tau at three different sites and NF-H/M werehigher in Ex9-39group than those in CON group.Comparing with DPP-4I+W group,the results of the phosphorylated levelsshowed the same changes in DPP-4I+W+Ex9-39group.(3)Comparing with CON group,the expression levels ofphosphorylated PI3K,Akt and GSK3βincreased significantly in DPP-4I group,while those decreased in W group.Additionally,the expression levels of phosphorylated PI3K,