关于心脏骤停猪模型复苏后 Alda-1 使用抑制铁死亡对脑损伤的研究
摘要
其脑氧微循环系统中铁死亡（Ferroptosis）的发生机制及其对脑组织损伤的影响。研究通过构建稳定的 CA-CPR 猪模型，
结合生化检测、组织病理学分析及先进的分子生物学技术，详细评估了乙醛脱氢酶 2（Aldehyde Dehydrogenase 2, ALDH2）
特异性激活剂 Alda-1 在减轻复苏后脑损伤中对铁死亡过程的调控作用。结果显示，Alda-1 的干预显著减轻了心脏骤停后
猪模型复苏过程中的脑组织损伤程度，这一保护作用可能与抑制长链脂酰辅酶 A 合成酶 4（ACSL4）以及上调谷胱甘肽过
氧化物酶 4（GPx4）的表达，进而阻断由铁死亡信号通路所介导的脑细胞程序性死亡过程有关。
关键词
全文:
PDF参考
[1]Lemiale V , Dumas F , Mongardon N ,et al. Intensive
care unit mortality after cardiac arrest: the relative contribution of
shock and brain injury in a large cohort[J]. Intensive Care Med,
2013,39(11):1972-1980. DOI: 10.1007/s00134-013-3043-4.
[2]Geocadin RG , Callaway CW , Fink EL ,et al. Standards
for studies of neurological prognostication in comatose survivors
of cardiac arrest: a scientific statement from the American Heart
Association[J]. Circulation, 2019,140(9):e517-e542. DOI:
10.1161/CIR.0000000000000702 .
[3]Panisello-Roselló A , Lopez A , Folch-Puy E ,et al. Role
of aldehyde dehydrogenase 2 in ischemia reperfusion injury: an
update[J]. World J Gastroenterol, 2018,24(27):2984-2994. DOI:
10.3748/wjg.v24.i27.2984 .
[4]Diao MY , Xu JF , Wang JG ,et al. Alda-1, an activator
of ALDH2, improves postresuscitation cardiac and neurological
outcomes by inhibiting pyroptosis in swine[J]. Neurochem Res,
2022,47(4):1097-1109. DOI: 10.1007/s11064-021-03511-x .
[5]Yuan H , Li XM , Zhang XY ,et al. Identification of
ACSL4 as a biomarker and contributor of ferroptosis[J]. Biochem
Biophys Res Commun, 2016,478(3):1338-1343. DOI: 10.1016/
j.bbrc.2016.08.124.
[6]Stockwell BR , Friedmann Angeli JP , Bayir H ,et al.
Ferroptosis: a regulated cell death nexus linking metabolism,
redox biology, and disease[J]. Cell, 2017,171(2):273-285. DOI:
10.1016/j.cell.2017.09.021 .
[7]Xu JF , Zhang MH , Liu F ,et al. Mesenchymal stem
cells alleviate post-resuscitation cardiac and cerebral injuries
by inhibiting cell pyroptosis and ferroptosis in a swine model
of cardiac arrest[J]. Front Pharmacol, 2021,12:793829. DOI:
10.3389/fphar.2021.793829 .
[8]Berg RA , Otto CW , Kern KB ,et al. High-dose
epinephrine results in greater early mortality after resuscitation
from prolonged cardiac arrest in pigs: a prospective,
randomized study[J]. Crit Care Med, 1994,22(2):282-290. DOI:
10.1097/00003246-199402000-00020 .
[9]Fu SH , Zhang HF , Yang ZB ,et al. Alda-1 reduces
cerebral ischemia/reperfusion injury in rat through clearance of
reactive aldehydes[J]. Naunyn Schmiedebergs Arch Pharmacol,
2014,387(1):87-94. DOI: 10.1007/s00210-013-0922-8 .
[10] 缪文丽 , 李海玲 , 王弘道 , 等 . 神经元特异性烯醇
化酶和 S100 蛋白评估心脏停搏患者复苏后脑损伤的研究
[J]. 中国危重病急救医学 , 2007,19(12):749-752. DOI: 10.3760/
cma.j.issn.1003-0603.2007.12.013 .
[11]Chen YQ , Fan HY , Wang SJ ,et al. Ferroptosis: a novel
therapeutic target for ischemia-reperfusion injury[J]. Front Cell
Dev Biol, 2021,9:688605. DOI: 10.3389/fcell.2021.688605 .
(11 摘要 Views, 20 PDF Downloads)
Refbacks
- 当前没有refback。