DPP-4 Inhibitor Linagliptin is Neuroprotective in Hyperglycemic Mice with Stroke via the AKT/mTOR Pathway and Anti-apoptotic Effects  

作　　者：Gang Zhang Samuel Kim Xiaohuan Gu Shan Ping Yu Ling Wei 

机构地区：[1]Department of Anesthesiology,Emory University School of Medicine,Atlanta,GA 30322,USA [2]Department of Neurology,Children's Hospital of Nanjing Medical University,Nanjing 210000,China [3]Department of Neurology,Emory University School of Medicine,Atlanta,GA 30322,USA

出　　处：《Neuroscience Bulletin》2020年第4期407-418,共12页神经科学通报（英文版）

基　　金：supported by the John E. Steinhaus Endowment fund.

摘　　要：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-m TOR 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/m TOR pathway along with anti-apoptotic and anti-inflammatory mechanisms.Therefore, linagliptin may be considered as a therapeutic treatment for stroke patients with mild hyperglycemia.

关 键 词：Cerebral ISCHEMIA HYPERGLYCEMIA DPP-4 inhibitor LINAGLIPTIN NEUROPROTECTION 

分 类 号：R743.3[医药卫生—神经病学与精神病学]