谷胱甘肽过氧化酶4激动剂Fer-1对睡眠碎片化的老年小鼠术后认知功能障碍防治作用观察  

Preventive and therapeutic effect of GPX4 agonist Fer-1 on postoperative cognitive dysfunction induced by sleep fragment in aged mice

作　　者：周银 侍崇龙 金文杰[1] ZHOU Yin;SHI Chongong;JIN Wenjie(Department of Anesthesiology,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院麻醉科,南京210029

出　　处：《山东医药》2023年第30期34-38,共5页Shandong Medical Journal

基　　金：江苏省重点实验室开放课题资助项目(XZSYSKF2020039)。

摘　　要：目的 观察谷胱甘肽过氧化酶4(GPX4)激动剂Ferrostatin-1(Fer-1)对睡眠碎片化的老年雄性小鼠术后认知功能障碍(POCD)的防治作用,并探讨其可能作用机制。方法 (1)睡眠碎片化老年雄性小鼠POCD观察及GPX4、线粒体呼吸链相关指标检测:取24只老年C57BL/6雄性小鼠随机分为实验组和对照组,每组各12只。实验组小鼠于多平台水环境睡眠碎片化饲养3天,对照组小鼠正常睡眠3天,第4天时两组均行胫骨骨折加髓内固定术(TFS,POCD动物模型制备方法),术后第3天分别采用逃避恐惧实验和Y-maze迷宫实验评估两组小鼠的逃避恐惧能力、短期记忆能力。随后处死两组小鼠,取小鼠海马组织检测海马组织谷胱甘肽过氧化酶4(GPX4)、线粒体呼吸链复合物Ⅰ(ComplexⅠ)及活性氧簇(ROS),取小鼠脑组织测算线粒体呼吸链功能相关指标线粒体基础呼吸率、ADP激发呼吸率及最大呼吸率。(2)加入Fer-1的睡眠碎片化老年小鼠POCD观察及海马组织ROS检测:另取12只老年雄性小鼠分为1、2组,每组各6只。两组均于多平台水环境睡眠碎片化饲养3天,1组小鼠在睡眠碎片化同时腹腔注射10 mg/kg的Fer-1,1次/天,连续3天;2组腹腔注射同体积的生理盐水,1次/天,连续3次。第4天时两组行TFS手术,TFS术后第3天采用逃避恐惧实验测试和Y-maze实验评估小鼠的逃避恐惧能力和短期记忆能力,利用线粒体荧光探针Mito SOX测算海马组织ROS。结果 与对照组比较,术后第3天实验组小鼠僵直反应时间短、进入新颖臂百分比低、海马组织GPX4相对表达量低(P均<0.05);与对照组比较,术后第3天实验组小鼠脑组织线粒体基础呼吸率低、ADP激发呼吸率低、最大呼吸率低,海马组织ComplexⅠ活性低、ROS含量高(P均<0.05)。与2组比较,术后第3天1组小鼠僵直反应时间长、进入新颖臂百分比高、海马组织ROS含量低(P均<0.05)。结论 腹腔注射Fer-1可改善睡眠碎片化的老年雄�Objective To investigate the preventive and therapeutic effect of glutathione peroxidase 4(GPX4) agonist Ferrostatin-1(Fer-1) on postoperative cognitive dysfunction(POCD) induced by sleep fragment in aged male mice and to explore its potential mechanism.Methods(1) Observation of POCD and detection of GPX4 and indicators related with mitochondrial respiratory chain in aged male mice with sleep fragment:Twenty-four aged C57BL/6 male mice were randomly divided into the experimental group(12 mice) and control group(12 mice).The mice in the experimental group were treated with sleep fragment in the multi-platform water environment for 3 days,and the mice in the control group slept normally for 3 days.A day later,tibial fracture and intramedullary fixation(TFS,POCD animal model method) were performed in both groups.Fear escape test and Y-maze test were used to evaluate the ability of mice to escape from fear and short-term memory of mice in the two groups on the third day after surgery.Then the mice in the two groups were sacrificed,and the hippocampal tissues were collected to detect GPX4,mitochondrial respiratory chain ComplexⅠand reactive oxygen species(ROS).The brain tissues of the mice were collected to measure the basic respiration rate,ADP-stimulated respiration rate and maximum respiration rate,which were related to mitochondrial respiratory chain function.(2) Observation of POCD and the level of ROS in aged mice with sleep fragment added with Fer-1:another 12 aged male mice were divided into two groups,with 6 mice in each group.Mice in both groups were treated with sleep fragment in the multi-platform water environment for 3 days.Mice in one group were intraperitoneally injected with 10 mg/kg Fer-1 once a day for 3consecutive days during sleep fragmentation and mice in the other group were intraperitoneally injected with the same volume of normal saline once a day for 3 consecutive days.A day later,TFS was performed in the two groups.On the 3rd day after TFS,the fear escape test and Y-maze test were conducte

关 键 词：谷胱甘肽过氧化酶4 睡眠碎片化 术后认知功能障碍 线粒体呼吸链 线粒体呼吸链复合物Ⅰ 

分 类 号：R3[医药卫生—基础医学]