Tanshinone IIA Promotes Functional Recovery After Spinal Cord Injury by Inhibiting Neuron and Oligodendrocyte Ferroptosis Through the GPX4/ACSL4 Axis

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemical Research Pub Date : 2025-05-16 DOI:10.1007/s11064-025-04414-x

Luchun Xu, Guozheng Jiang, Shuyin Tan, Yukun Ma, Jiawei Song, Yushan Gao, Guanlong Wang, Jiaojiao Fan, Yongdong Yang, Xing Yu

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引用次数: 0

Abstract

Spinal cord injury (SCI) induces severe functional impairments and involves intricate secondary injury mechanisms. Tanshinone IIA (TIIA), a key bioactive component of Salvia miltiorrhiza, exhibits neuroprotective potential, yet its role in ferroptosis regulation post-SCI remains undefined. This study explored the protective effects and underlying mechanisms of TIIA in SCI. In a rat SCI model, TIIA markedly enhanced hind limb motor function and preserved histopathological integrity while mitigating mitochondrial damage, ferroptosis, and oxidative stress. TIIA attenuated ferroptosis by reducing reactive oxygen species (ROS), malondialdehyde (MDA), and acyl-CoA synthetase long-chain family member 4 (ACSL4) while elevating glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase 4 (GPX4) levels. Mechanistically, TIIA suppressed ferroptosis through modulation of the GPX4/ACSL4 axis. The ferroptosis inducer RSL3 abrogated these protective effects, further validating this mechanism. These findings highlight the therapeutic potential of TIIA in SCI by targeting the GPX4/ACSL4 pathway to attenuate ferroptosis and promote functional recovery.

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丹参酮IIA通过GPX4/ACSL4轴抑制神经元和少突胶质细胞铁下垂促进脊髓损伤后功能恢复

脊髓损伤引起严重的功能损伤，涉及复杂的继发性损伤机制。丹参酮IIA （TIIA）是丹参的一种重要生物活性成分，具有一定的神经保护作用，但其在脊髓损伤后铁吊中的作用尚不清楚。本研究探讨了TIIA对脊髓损伤的保护作用及其机制。在大鼠脊髓损伤模型中，TIIA显著增强后肢运动功能，保持组织病理学完整性，同时减轻线粒体损伤、铁下垂和氧化应激。TIIA通过降低活性氧（ROS）、丙二醛（MDA）和酰基辅酶a合成酶长链家族成员4 (ACSL4)，同时提高谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶4 （GPX4）水平来减轻铁下垂。在机制上，TIIA通过调节GPX4/ACSL4轴抑制铁下垂。铁下垂诱导剂RSL3消除了这些保护作用，进一步证实了这一机制。这些发现强调了TIIA通过靶向GPX4/ACSL4通路来减轻铁下垂和促进功能恢复在脊髓损伤中的治疗潜力。

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来源期刊

Neurochemical Research 医学-神经科学

CiteScore

7.70

自引率

2.30%

发文量

320

审稿时长

6 months

期刊介绍： Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.