Wang Mengwei, Luo Le
Department of Emergency, The Fourth Affiliated Hospital of China Medical University, No. 4 Chongshan East Road, Huanggu District, Shenyang, 110032, Liaoning, China.
Shanghai Zhuole Biotechnology Center, No. 2066 Wangyuan Road, Shanghai, 201499, China.
Neurochem Res. 2020 May;45(5):1097-1106. doi: 10.1007/s11064-020-02987-3. Epub 2020 Feb 18.
Traumatic brain injury (TBI) has become a leading cause of death and disability all over the world. Pharmacological suppression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) can inhibit oxidative stress which is implicated in the pathology of TBI. GSK2795039 was reported to target NOX2 to inhibit [Formula: see text] and ROS production. The present study aimed to investigate the effect of GSK2795039 on NOX2 activity and neurological deficits in a TBI mouse model. TBI mouse model was established by a weight-drop to mouse skull. GSK2795039 at a dose of 100 mg/kg was administrated to mice 30 min before TBI. NOX2 expression and activity were detected by Western blot and biochemical method. Neurological damage and apoptosis were detected by behavioral test and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. GSK2795039 significantly inhibited NOX2 expression and activity in the TBI mouse model. It also attenuated TBI-induced neurological deficits, apoptosis, and neurological recovery. The results indicate that GSK2795039 can be used as a potential drug for TBI treatment.
创伤性脑损伤（TBI）已成为全球死亡和残疾的主要原因。药理学抑制烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶2（NOX2）可抑制与TBI病理学相关的氧化应激。据报道，GSK2795039靶向NOX2以抑制[公式：见正文]和活性氧（ROS）生成。本研究旨在探讨GSK2795039对TBI小鼠模型中NOX2活性和神经功能缺损的影响。通过向小鼠颅骨滴加重物建立TBI小鼠模型。在TBI前30分钟给小鼠施用剂量为100mg/kg的GSK2795039。通过蛋白质印迹法和生化方法检测NOX2表达和活性。通过行为测试和末端脱氧核苷酸转移酶dUTP缺口末端标记染色检测神经损伤和细胞凋亡。GSK2795039在TBI小鼠模型中显著抑制NOX2表达和活性。它还减轻了TBI诱导的神经功能缺损、细胞凋亡和神经恢复。结果表明，GSK2795039可作为TBI治疗的潜在药物。
