外泌体通过NRF2/SLC7A11/GPX4通路调控铁死亡治疗小鼠缺血性脑卒中

徐英韬, 王蒙蒙, 林平, 迟海涛, 王怡, 白鹰

Exosomes Treat Ischemic Stroke by Regulation of Ferroptosis Through the NRF2/SLC7A11/GPX4 Pathway in Mice

XU Yingtao, WANG Mengmeng, LIN Ping, CHI Haitao, WANG Yi, BAI Ying

图6 各组小鼠脑组织中NRF2、SLC7A11、GPX4 mRNA及蛋白表达检测分析结果 注：A~C，各组小鼠脑组织中核因子-红细胞系2相关因子2（NRF2）、溶质载体家族7成员11（SLC7A11）和谷胱甘肽过氧化物酶4（GPX4）的mRNA转录水平分析；D~F，各组小鼠脑组织中NRF2、SLC7A11和GPX4蛋白相对表达量分析；G，各组小鼠脑组织中NRF2、SLC7A11、GPX4和GAPDH的蛋白质印迹结果图。假手术组（Sham）只暴露大脑中动脉，不电凝血管；模型组（MCAO）使用高频手术镊以8 W功率电凝大脑中动脉；模型+生理盐水组（MCAO+NaCl）先通过尾静脉注射100 μL生理盐水，然后进行电凝法造模；模型+外泌体组（MCAO+EXO）先通过尾静脉注射100 μL来自人羊膜间充质干细胞（hAMSCs）培养上清液的外泌体（9.5×1011个/mL），然后进行电凝法造模。每组小鼠各8只，?P＜0.05，??P＜0.01，???P＜0.001，????P＜0.000 1。

Figure 6 Detection and analysis of mRNA and protein expression of NRF2， SLC7A11 and GPX4 in the brains of each group of mice Note： A-C， mRNA transcription levels of nuclear factor-erythroid 2-related factor 2 （NRF2）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in the brains of mice from each group. D-F， Relative protein expression levels of NRF2， SLC7A11， and GPX4 in the brains of mice from each group. G， Western blotting images of NRF2， SLC7A11， GPX4， and GAPDH. The sham operation group （Sham） only exposed the middle cerebral artery without electrocoagulation of the vessel； the model group （MCAO） used high-frequency surgical forceps to electrocoagulate the middle cerebral artery at a power of 8 W； the model + normal saline group （MCAO+NaCl） first injected 100 μL of normal saline through the tail vein， and then performed electrocoagulation modeling； the model + exosome group （MCAO+EXO） first injected 100 μL of exosomes （9.5×1011 particles per mL） from the culture supernatant of human amniotic mesenchymal stem cells （hAMSCs） through the tail vein， and then performed electrocoagulation modeling. There were eight mice in each group. ?P<0.05， ??P<0.01， ???P<0.001， ????P<0.000 1.