Yan Rongbao, Yuan Ye, Shi Ce, Li Yang, Li Yang, Wang Wenbo, Yang Lei
Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, China; NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Pharmacy (The University Key Laboratory of Drug Research, Heilongjiang Province), The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Int Immunopharmacol. 2025 Apr 24;153:114401. doi: 10.1016/j.intimp.2025.114401. Epub 2025 Mar 17.
Neuroinflammation is essential for intricate pathophysiologic mechanisms after spinal cord injury (SCI). Increasing evidence suggests that anthraquinones possess anti-inflammatory properties in central nervous system (CNS) disorders. However, the effects of Kanglexin (Klx), a novel synthetic anthraquinone compound, on SCI remain unknown.
C57BL/6 mice were utilized to establish a contused SCI model to explore the in vivo neuroprotective and inflammatory modulatory effects of Klx. An inflammation model was also created in vitro using BV2 cells. Neuroprotective effects were assessed by evaluating motor function and neuropathologic alterations. Inflammation modulation was analyzed through markers of polarization and pyroptosis, with further mechanistic insights obtained via transcriptome sequencing.
Klx facilitated the recovery of hindlimb locomotor function and improved neuronal survival after SCI. Both in vitro and in vivo assays revealed that Klx inhibited NLRP3 inflammasome-induced pyroptosis. In addition, Klx promoted the polarization of microglia from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Mechanistically, Klx enhanced PKA phosphorylation and suppressed NF-κB and IκBα phosphorylation, thereby reducing NF-κB nuclear translocation.
Klx demonstrated neuroprotective and inflammation-modulating effects on SCI, suggesting that it might offer a promising therapeutic alternative for SCI.
神经炎症在脊髓损伤（SCI）后的复杂病理生理机制中至关重要。越来越多的证据表明，蒽醌类化合物在中枢神经系统（CNS）疾病中具有抗炎特性。然而，新型合成蒽醌化合物康络欣（Klx）对脊髓损伤的影响尚不清楚。
利用C57BL/6小鼠建立脊髓挫伤模型，以探究Klx的体内神经保护和炎症调节作用。还使用BV2细胞在体外建立炎症模型。通过评估运动功能和神经病理改变来评估神经保护作用。通过极化和细胞焦亡标记物分析炎症调节，并通过转录组测序获得进一步的机制见解。
Klx促进脊髓损伤后后肢运动功能的恢复并改善神经元存活。体外和体内试验均表明，Klx抑制NLRP3炎性小体诱导的细胞焦亡。此外，Klx促进小胶质细胞从促炎M1表型向抗炎M2表型极化。机制上，Klx增强PKA磷酸化并抑制NF-κB和IκBα磷酸化，从而减少NF-κB核转位。
Klx对脊髓损伤具有神经保护和炎症调节作用，表明它可能为脊髓损伤提供一种有前景的治疗选择。
