GRSF1/GPX4轴调控的铁代谢紊乱在小鼠脑缺血再灌注损伤中的作用  

Role of Iron Metabolism Disorder Regulated by GRSF1/GPX4 Axis in Cerebral Ischemia-reperfusion Injury in mice

作　　者：刘雅静[1] 李亚男 李冰玉 王苏[1] 刘恋[1] LIU Yajing;LI Yanan;LI Bingyu(Department of Anesthesiology,Renmin Hospital of Wuhan University,Hubei 430060,China)

机构地区：[1]武汉大学人民医院麻醉科,430060

出　　处：《医学研究杂志》2024年第3期34-37,49,共5页Journal of Medical Research

基　　金：国家自然科学基金资助项目(82102295)。

摘　　要：目的探讨GRSF1/GPX4轴调控的铁代谢紊乱在小鼠脑缺血再灌注损伤中的作用。方法清洁级雄性C57BL/6小鼠18只,采用随机数字表法将其分为假手术组、脑缺血再灌注组、脑缺血再灌注+GRSF1过表达组,每组各6只。脑缺血再灌注组采用线栓法制备小鼠脑缺血再灌注损伤模型;脑缺血再灌注+GRSF1过表达组于造模前7天注射GRSF1过表达慢病毒。再灌注24h后行神经功能评分,TUNEL法检测细胞凋亡率,Western blot法检测GRSF1、GPX4、IRP2、TfR1和铁蛋白表达水平。结果与假手术组比较,脑缺血再灌注组神经功能评分、凋亡率、IRP2、TfR1、铁蛋白表达水平升高,GRSF1、GPX4表达水平降低(P<0.05);与脑缺血再灌注组比较,脑缺血再灌注+GRSF1过表达组神经功能评分、凋亡率、IRP2、TfR1、铁蛋白表达水平降低,GRSF1、GPX4表达水平升高(P<0.05)。结论过表达GRSF1通过上调GPX4抑制铁离子代谢紊乱进而减轻小鼠脑缺血再灌注损伤。Objective To investigate the role of iron metabolism disorder regulated by GRSF1/GPX4 axis in cerebral ischemia-reperfusion injury in mice.Methods A total of 18 clean grade male C57BL/6mice were randomly divided into 3groups:sham operation group,cerebral ischemia-reperfusion group,cerebral ischemia-reperfusion+GRSF1 overexpression group,with 6mice in each group.The model of cerebral ischemia-reperfusion was established by thread occlusion in cerebral ischemia-reperfusion group,and GRSF1 overexpressed lentivirus was injected in cerebral ischemia-reperfusion+GRSF1 overexpression group 7days before modeling.After 24h of reperfusion,the neurological function score was evaluated,apoptosis rate of brain tissue was detected by TUNEL method,and the protein expression levels of GRSF1,GPX4,IRP2,TfR1 and ferritin were detected by Western blotting method.Results Compared with sham operation group,the neurological function score,apoptosis rate were increased as well as the expression levels of IRP2,TfR1 and ferritin in cerebral ischemia-reperfusion group,while GRSF1,GPX4 expression levels were decreased(P<0.05).Compared with cerebral ischemia-reperfusion group,the neurological function score,apoptosis rate,the expression levels of IRP2,TfR1 and ferritin were decreased in cerebral ischemia-reperfusion+GRSF1 overexpression group,while GRSF1 and GPX4 expression levels were increased(P<0.05).Conclusion Overexpression of GRSF1 attenuates cerebral ischemia-reperfusion injury in mice by up-regulating GPX4 to inhibit iron metabolism disorder.

关 键 词：GRSF1 GPX4 铁代谢 脑缺血再灌注损伤 

分 类 号：R614[医药卫生—麻醉学]