SPP1通过促进ferroptosis诱导的大脑损伤来加剧缺血性中风
Yunfei Zhou1, Longxiao Zhang1, Xinyang Yan2
1Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China; Center for Precision Cancer Medicine, MED-X Institute, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 712000, Shaanxi Province, China.
Biochemical and biophysical research communications
|September 16, 2025
概括
通过调节PI3K/AKT通路,SPP1抑制可缓解脑缺血中的铁和神经元死亡. 这一发现将SPP1确定为缺血性中风治疗的潜在治疗标.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 缺血性中风是全球死亡和残疾的主要原因.
- 反应性氧物种 (ROS) 和铁亡与大脑缺血 - 反 (I/R) 损伤有关.
- SPP1 (分泌的蛋白1) 与I/R损伤中的ROS积累有关.
研究的目的:
- 研究SPP1和脑缺血中的铁化之间的关系.
- 阐明涉及SPP1介导的神经元损伤的下游信号通路.
- 评估SPP1作为缺血性中风的潜在治疗点.
主要方法:
- 在HT22细胞中利用氧-葡萄糖剥夺/再氧化 (OGD/R),在小鼠模型中利用中脑动脉封闭/再输液 (MCAO/R).
- 分析了SPP1的表达,使用西方斑点和免疫光.
- 使用的Spp1敲击细胞/小鼠和SPP1特异性抑制剂 (化合物11).
- 研究PI3K/AKT通路和铁亡标记物 (例如ACSL4).
- 进行ROS量化和电子显微镜.
主要成果:
- 在 ischemia-reperfusion 后,SPP1 的表达增加.
- 在OGD/R和MCAO/R模型中,SPP1抑制显著缓解了铁亡和神经元死亡.
- 通过PI3K/AKT信号通路,SPP1调节神经元死亡,在SPP1敲击时,p-PI3K和p-AKT水平降低.
- 抑制PI3K逆转了SPP1过度表达引起的铁亡,并减少了ACSL4的表达.
结论:
- 在大脑缺血期间,SPP1在促进铁和神经元损伤方面发挥着关键作用.
- 调节PI3K/AKT通路是SPP1发挥其作用的关键机制.
- 抑制SPP1是治疗脑缺血的一个有前途的治疗策略.
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