SIRT1/Nrf2/HO-1通路在七氟烷后处理改善失血性休克复苏小鼠空间学习与记忆障碍中的作用  

Role of SIRT1/Nrf2/HO-1 pathway in attenuation of learning and memory impairment by sevoflurane postcondition in a mouse model of hemorrhagic shock and resuscitation

作　　者：牛志伦 张丽 胡溯 吴雨洁 万晓静 胡宪文[1] NIU Zhi-lun;ZHANG Li;HU Su;WU Yu-jie;WAN Xiao-jing;HU Xian-wen(Dept of Anesthesiology and Perioperative Medicine,the Second Affiliated Hospital of Anhui Medical University,Hefei 230601,China)

机构地区：[1]安徽医科大学第二附属医院麻醉与围术期医学科,安徽合肥230601

出　　处：《中国药理学通报》2024年第3期551-556,共6页Chinese Pharmacological Bulletin

基　　金：安徽省高校自然科学重大研究项目(NoKJ2021ZD0030);安徽省重点研究与开发项目(No2022e07020045);安医大二附院临床培育计划重点项目(No2021LCZD02)。

摘　　要：目的探究沉默信息调节因子1(silent information regulation 1,SIRT1)/核因子E2相关因子2(nuclear transcription factor E2 related factor 2,Nrf2)/血红素加氧酶-1(heme oxygenase 1,HO-1)通路在七氟烷后处理减轻脑缺血/再灌注小鼠认知功能损伤中的作用。方法将♂C57BL/6J小鼠随机分为:假手术组、失血性休克复苏组、七氟烷后处理组、七氟烷后处理+SIRT1抑制剂组、七氟烷后处理+Nrf2抑制剂组,建立脑缺血/再灌注模型。水迷宫检验小鼠学习记忆能力;检测海马组织ATP、超氧化物歧化酶(superoxide dismutase,SOD)、活性氧、丙二醛含量;Western blot检测海马SIRT1、Nrf2和HO-1蛋白表达。结果再灌注后小鼠学习记忆能力降低,海马SOD、ATP含量降低,丙二醛、活性氧含量升高,SIRT1、Nrf2和HO-1蛋白表达降低;七氟烷处理后减轻了再灌注后小鼠记忆障碍和氧化应激;加用SIRT1和Nrf2抑制剂后,减弱了七氟烷对小鼠认知障碍和氧化损伤的保护作用。结论七氟烷后处理可能通过SIRT1/Nrf2/HO-1通路对失血性休克复苏引起的小鼠学习记忆障碍起到保护作用,机制与其抑制氧化应激反应相关。Aim To explore the role of SIRT1/Nrf2/HO-1 in alleviating the cognitive function impairment by sevoflurane treatment in a mouse model of postoperative cerebral reperfusion.Methods C57BL/6J mice were randomly divided into five groups:sham operation group,hemorrhagic shock reperfusion group,sevoflurane postconditioning group,sevoflurane postconditioning+SIRT1 inhibitor group and sevoflurane postconditioning+Nrf2 inhibitor group.Mice were subjected to Morris water maze test after cerebral ischemia reperfusion.The ATP,superoxide dismutase(SOD),ROS and MDA contents in tissue of mice were detected.SIRT1,Nrf2 and HO-1 proteins in tissue were detected by Western blot.Results After hemorrhagic shock,the learning and memory ability of mice was reduced.ATP and SOD concentration in hippocampus was reduced,MDA and ROS concentration increased,and the SIRT,Nrf2 and HO-1 concentration was reduced.Sevoflurane improved the cognitive dysfunction and oxidative damage in postoperative mice,and the neuroprotective effect of sevoflurane on hemorrhagic shock and resuscitation mice was weakened followed with SIRT1 and Nrf2 inhibitors.Conclusion Sevoflurane probably alleviates the oxidative reaction damage and cognitive impairment caused by cerebral reperfusion in mice through SIRT1/Nrf2/HO-1 pathway.

关 键 词：七氟烷后处理 失血性休克复苏 SIRT1 NRF2 HO-1 水迷宫 氧化应激 

分 类 号：R-332[医药卫生] R322.81R338.64R605.971R614