Dipeptidyl peptidase 4 (DPP-4) inhibitors have been shown to have neuroprotective effects in diabetic patients suffering from stroke, but less research has focused on patients with mild hyperglycemia below the threshold for a diagnosis of diabetes. In this investigation, a hyperglycemic mouse model was generated by intraperitoneal injection of streptozotocin and then subjected to focal cerebral ischemia. We demonstrated that the DPP-4 inhibitor linagliptin significantly decreased the infarct volume, reduced neuronal cell death, decreased inflammation, and improved neurological deficit compared with control mice. Linagliptin up-regulated the expression of p-Akt and p-mTOR and regulated the apoptosis factors Bcl-2, Bax, and caspase 9. Taken together, these results suggest that linagliptin exerts a neuroprotective action likely through activation of the Akt/mTOR pathway along with anti-apoptotic and anti-inflammatory mechanisms. Therefore, linagliptin may be considered as a therapeutic treatment for stroke patients with mild hyperglycemia.

中文翻译：

---

DPP-4抑制剂利格列汀通过AKT / mTOR途径对中风的高血糖小鼠具有神经保护作用，并具有抗凋亡作用。

二肽基肽酶4（DPP-4）抑制剂已显示对患有中风的糖尿病患者具有神经保护作用，但针对轻度高血糖症低于诊断糖尿病阈值的患者的研究较少。在这项研究中，通过腹膜内注射链脲佐菌素产生高血糖小鼠模型，然后进行局部脑缺血。我们证明，与对照小鼠相比，DPP-4抑制剂利格列汀显着降低了梗塞体积，减少了神经元细胞死亡，减少了炎症并改善了神经功能缺损。利格列汀上调p-Akt和p-mTOR的表达，并调节细胞凋亡因子Bcl-2，Bax和caspase 9。这些结果表明，利格列汀可能通过激活Akt / mTOR途径以及抗凋亡和抗炎机制发挥神经保护作用。因此，利那列汀可被视为轻度高血糖卒中患者的治疗方法。