Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage
Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage
复制标题
选择性铁死亡抑制剂 Liproxstatin-1 可减轻蛛网膜下腔术后神经功能缺损和神经炎症
DOI：
10.1007/s12264-020-00620-5
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发表时间：
2021-01-09
影响因子：
5.6
通讯作者：
Wang, Lin
中科院分区：
文献类型：
--
作者：
Cao, Yang;Li, Yin;Wang, Lin
铁凋亡是铁依赖性调节细胞死亡的一种形式。其存在的证据及其抑制剂对蛛网膜下腔出血（SAH）的影响仍然缺乏。在本研究中，我们发现livestatin-1保护HT 22细胞对氯化血红素诱导的损伤，通过保护线粒体功能和改善脂质过氧化。在体内实验中，我们证明了在SAH后同侧皮层神经元中存在特征性萎缩线粒体。此外，livestatin-1减轻神经功能缺损和脑水肿，减少神经元细胞死亡，并恢复SAH后的氧化还原平衡。利司他汀-1对铁凋亡的抑制与谷胱甘肽过氧化物酶4的保护和酰基辅酶A合成酶长链家族成员4以及环氧合酶2的下调有关。此外，livestatin-1减少了小胶质细胞的活化和IL-6、IL-1 β和TNF-α的释放。这些数据增强了我们对SAH后细胞死亡的理解，并为未来的临床前研究提供了线索。
Ferroptosis is a form of iron-dependent regulated cell death. Evidence of its existence and the effects of its inhibitors on subarachnoid hemorrhage (SAH) is still lacking. In the present study, we found that liproxstatin-1 protected HT22 cells against hemin-induced injury by protecting mitochondrial functions and ameliorating lipid peroxidation. In in vivo experiments, we demonstrated the presence of characteristic shrunken mitochondria in ipsilateral cortical neurons after SAH. Moreover, liproxstatin-1 attenuated the neurological deficits and brain edema, reduced neuronal cell death, and restored the redox equilibrium after SAH. The inhibition of ferroptosis by liproxstatin-1 was associated with the preservation of glutathione peroxidase 4 and the downregulation of acyl-CoA synthetase long-chain family member 4 as well as cyclooxygenase 2. In addition, liproxstatin-1 decreased the activation of microglia and the release of IL-6, IL-1 beta, and TNF-alpha. These data enhance our understanding of cell death after SAH and shed light on future preclinical studies.