Li Wenxiang, Zhao Xiaoqing, Zhang Rong, Liu Xinjie, Qi Zhangyang, Zhang Yang, Yang Weiqi, Pang Yilin, Zhao Chenxi, Fan Baoyou, Ran Ning, Zhang Jiawei, Kong Xiaohong, Feng Shiqing, Yao Xue
Shandong University Center for Orthopedics, Department of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.
Tianjin Key Laboratory of Spine and Spinal Cord, National Spinal Cord Injury International Cooperation Base, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China.
Neural Regen Res. 2023 Nov;18(11):2474-2481. doi: 10.4103/1673-5374.371377.
Maintaining the integrity of the blood-spinal cord barrier is critical for the recovery of spinal cord injury. Ferroptosis contributes to the pathogenesis of spinal cord injury. We hypothesized that ferroptosis is involved in disruption of the blood-spinal cord barrier. In this study, we administered the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal cord injury in rats. Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord injury. Liproxstatin-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction protein. Liproxstatin-1 inhibited ferroptosis of endothelial cell after spinal cord injury, as shown by the immunofluorescence of an endothelial cell marker (rat endothelium cell antigen-1, RECA-1) and ferroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase. Liproxstatin-1 reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase. Furthermore, inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment. In summary, liproxstatin-1 improved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-spinal cord barrier integrity.
维持血脊髓屏障的完整性对脊髓损伤的恢复至关重要。铁死亡促成脊髓损伤的发病机制。我们推测铁死亡参与了血脊髓屏障的破坏。在本研究中，我们在大鼠脊髓挫伤后腹腔注射铁死亡抑制剂liproxstatin-1。Liproxstatin-1改善了脊髓损伤后的运动恢复和体感诱发电位电生理表现。Liproxstatin-1通过上调紧密连接蛋白的表达来维持血脊髓屏障的完整性。如内皮细胞标志物（大鼠内皮细胞抗原-1，RECA-1）和铁死亡标志物酰基辅酶A合成酶长链家族成员4及15-脂氧合酶的免疫荧光所示，Liproxstatin-1抑制脊髓损伤后内皮细胞的铁死亡。Liproxstatin-1通过上调谷胱甘肽过氧化物酶4并下调酰基辅酶A合成酶长链家族成员4和15-脂氧合酶，在体外减少脑内皮细胞铁死亡。此外，liproxstatin-1治疗后炎症细胞募集和星形胶质细胞增生得到缓解。总之，liproxstatin-1通过抑制内皮细胞铁死亡和维持血脊髓屏障的完整性改善脊髓损伤恢复。
