Polydatin alleviates traumatic brain injury: Role of inhibiting ferroptosis
Polydatin alleviates traumatic brain injury: Role of inhibiting ferroptosis
复制标题
虎杖甙减轻创伤性脑损伤：抑制铁死亡的作用
DOI：
10.1016/j.bbrc.2021.03.108
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发表时间：
2021-04-08
影响因子：
3.1
通讯作者：
Feng, Dayun
中科院分区：
文献类型：
--
作者：
Huang, Lu;He, Shulei;Feng, Dayun
继发性损伤是脑外伤死亡率高、预后差的主要原因，近年来研究认为与脑外伤后的铁中毒有关。白藜芦醇苷是一种从蓼属植物根茎中提取的单晶化合物，已被证明具有潜在的神经保护作用。然而，其在TBI继发性损伤中的作用和机制尚未阐明。本研究观察了白藜芦醇苷对体外培养的Neuro 2A细胞和TBI小鼠模型铁凋亡的抑制作用，其特征是逆转游离Fe-2（+）的积累或沉积，增加MDA含量，降低关键氧化还原酶GPx 4的活性，导致细胞死亡和组织丢失。虽然虎杖苷纠正了TBI后铁凋亡信号分子GPX 4，SLC 7A 11，PTGS 2和ATP 5G 3的mRNA水平增加，但TBI和虎杖苷处理对其蛋白表达没有显著影响。值得注意的是，虎杖苷在体内和体外都能完全逆转TBI后GPx 4活性的下降，并且在体外的作用强于经典的铁凋亡抑制剂FER-1。此外，虎杖苷已被证明可以降低TBI小鼠中急性神经损伤的严重程度并显著改善亚急性运动功能障碍。我们的研究结果提供了翻译的洞察力与白藜芦醇苷在TBI的神经保护作用，通过抑制铁凋亡主要依赖于GPx 4活性的维持。(C)2021年由Elsevier Inc.出版
Secondary injury is the main cause of high mortality and poor prognosis of TBI, which has recently been suggested to be related to ferroptosis. Polydatin, a monocrystalline compound extracted from the rhizome of Polygonum, has been shown to exert potential neuroprotective effects. However, its role and mechanism in the secondary injury of TBI has not been elucidated. In this study, the inhibition of Polydatin on ferroptosis was observed both in the hemoglobin treated Neuro2A cells in vitro and in TBI mouse model in vivo, characterized by reversion of accumulation or deposition of free Fe-2(+), increased content of MDA, decreased activity of key REDOX enzyme GPx4, cell death and tissues loss. Although Polydatin corrected the increased mRNA levels of ferroptosis signaling molecules GPX4, SLC7A11, PTGS2, and ATP5G3 after TBI, TBI and Polydatin treatment had no significant effect on their protein expression. Notably, Polydatin could completely reverse the decrease of GPx4 activity after TBI in vivo and in vitro, and the effect was stronger than that of the classical ferroptosis inhibitor FER-1 in vitro. Further, Polydatin has been shown to reduce the severity of acute neurological impairment and significantly improve subacute motor dysfunction in TBI mice. Our findings provided translational insight into neuroprotection with Polydatin in TBI by inhibiting ferroptosis mainly depending on the maintenance of GPx4 activity. (C) 2021 Published by Elsevier Inc.