布美他尼对小鼠心搏骤停后脑损伤的保护作用

The protective effects of bumetanide on post-cardiac arrest brain injury in mice

目的探讨布美他尼(Bumetanide,BUM)是否可以减轻心搏骤停后脑损伤。方法建立小鼠心搏骤停/心肺复苏(Cardiac arrest/cardiopulmonary resuscitation,CA/CPR)模型,经静脉给予2 mg/kg BUM处理;对照组给予等量生理盐水(Vehicle,Veh)处理;在术后24 h监测小鼠生存率,对小鼠进行神经功能评分和运动功能评分;对小鼠脑切片进行组织病理学检查,用苏木素-伊红(Haematoxylin-eosin,HE)染色检测小鼠脑组织病理学变化,用Fluoro-Jade B染色评估小鼠神经元退行性变情况,用胶质纤维酸性蛋白(Glial fibrillary acidic protein,GFAP)/离子钙接头蛋白抗原(Ionized calcium bindingadaptor molecule-1,Iba-1)染色评估小鼠脑组织炎症反应,用二氢乙啶染色评估小鼠脑活性氧产生。结果CA/CPR使小鼠生存率降低,并出现明显脑损伤,表现为神经功能评分降低、运动功能评分降低、神经元死亡增加、神经炎症反应强烈和活性氧产生增加;与对照组比较,BUM可明显提高CA/CPR后生存率,并改善上述脑损伤表现。结论BUM可提高CA/CPR后生存率并减轻心搏骤停后脑损伤。

Objective To investigate whether treatment with bumetanide could alleviate brain injury after cardiac arrest.Methods A mouse cardiac arrest/cardiopulmonary resuscitation(CA/CPR)model was established,and 2 mg/kg bumetanide was given intravenously.The control group was treated with the same amount of normal saline(vehicle,Veh).The survival rate of mice was monitored 24 hours after operation,and the neurological function and motor function were scored.Histopathological examination was performed on mouse brain sections.HE staining was used to detect brain histopathological changes,Fluoro-Jade B staining was used to evaluate neuronal degeneration,GFAP/Iba-1 staining was used to evaluate brain inflammation,and dihydroethidium staining was used to evaluate brain reactive oxygen species production.Results CA/CPR resulted in decreased survival and significant brain injury in mice,which was characterized by decreased neurological function score,decreased motor function score,increased neuronal death,strong neuroinflammatory response,and increased production of reactive oxygen species.Compared with the control group,bumetanide could significantly improve survival after CA/CPR and improve the above brain injury manifestations.Conclusion Bumetanide could improve survival rate after CA/CPR and alleviate post-cardiac arrest brain injury.