Department of Preventive Health, The 3rd People's Hospital of Xiangcheng District, Suzhou, Jiangsu 215134, P.R. China.
Department of Basic Courses, Computer Teaching and Research Section, Suzhou Vocational Health College, Suzhou, Jiangsu 215009, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4113-4119. doi: 10.3892/mmr.2017.8289. Epub 2017 Dec 18.
Diabetes has been identified to be a risk factor for Alzheimer's disease (AD). Vildagliptin, a novel oral hypoglycemic agent, has been demonstrated to exert protective effects on the pancreas and cardiovascular system. The present study examined the potential protective effects of vildagliptin on neurons in an AD rat model. Treatment with vildagliptin improved memory deficits and decreased neuronal apoptosis in the hippocampus. The expression levels of B cell lymphoma 2 (Bcl‑2) were increased, and the expression levels of caspase‑3, Bcl‑2 associated X protein and AD‑associated proteins were decreased in the hippocampus following treatment with vildagliptin. Additionally, the AD model‑induced decrease in phosphorylated (p) protein kinase B (p‑Akt), p‑glycogen synthase kinase 3β (p‑GSK3β), post‑synaptic density 95 and synaptophysin expression was reversed. These results indicate that vildagliptin administration exerts a protective effect against cognitive deficits by reducing tau phosphorylation and increasing the expression of proteins associated with synaptic plasticity in the hippocampus. Targeting of the Akt/GSK3β signaling pathway may be a key mechanism in preventing the disease progression of AD.
糖尿病已被确定为阿尔茨海默病（AD）的一个风险因素。维格列汀是一种新型的口服降糖药，已被证明对胰腺和心血管系统具有保护作用。本研究探讨了维格列汀对 AD 大鼠模型神经元的潜在保护作用。维格列汀治疗可改善记忆障碍，并减少海马区神经元凋亡。维格列汀治疗后，B 细胞淋巴瘤 2（Bcl-2）的表达水平增加，而半胱天冬酶-3、Bcl-2 相关 X 蛋白和 AD 相关蛋白的表达水平降低。此外，AD 模型诱导的磷酸化蛋白激酶 B（p-Akt）、磷酸化糖原合成酶激酶 3β（p-GSK3β）、突触后密度 95 和突触小体素表达的降低也得到了逆转。这些结果表明，维格列汀通过减少 tau 磷酸化和增加与海马突触可塑性相关蛋白的表达，对认知功能障碍发挥保护作用。靶向 Akt/GSK3β 信号通路可能是预防 AD 疾病进展的关键机制。
