Xu Luchun, Jiang Guozheng, Tan Shuyin, Ma Yukun, Song Jiawei, Gao Yushan, Wang Guanlong, Fan Jiaojiao, Yang Yongdong, Yu Xing
Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, PR China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102401, PR China.
Neurochem Res. 2025 May 16;50(3):167. doi: 10.1007/s11064-025-04414-x.
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.
脊髓损伤（SCI）会导致严重的功能障碍，并涉及复杂的继发性损伤机制。丹参酮IIA（TIIA）是丹参的关键生物活性成分，具有神经保护潜力，但其在脊髓损伤后铁死亡调节中的作用仍不明确。本研究探讨了TIIA对脊髓损伤的保护作用及其潜在机制。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、铁死亡和氧化应激。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）水平来减轻铁死亡。机制上，TIIA通过调节GPX4/ACSL4轴抑制铁死亡。铁死亡诱导剂RSL3消除了这些保护作用，进一步验证了这一机制。这些发现突出了TIIA通过靶向GPX4/ACSL4途径减轻铁死亡并促进功能恢复在脊髓损伤治疗中的潜力。
