Wang Ji-Huan, Sheng Hong-Biao, Li Jun-Kun
Department of Orthopedics, Fengcheng Hospital of Fengxian District, Shanghai, People's Republic of China.
Kaohsiung J Med Sci. 2025 Sep;41(9):e70041. doi: 10.1002/kjm2.70041. Epub 2025 May 20.
This study aims to assess the therapeutic effectiveness of Relaxin-2 (RLN-2) in promoting functional recovery and neuroprotection following spinal cord injury (SCI) in mice. Furthermore, continuous subcutaneous infusion of Serelaxin (0.5 mg/kg/day; human recombinant relaxin-2) improved neurological recovery, as evidenced by higher Basso-Beattie-Bresnahan (BBB) scores and reduced foot-stepping angles compared to the SCI group. Additionally, RLN-2 effectively reduced edema in the injured spinal cord, as shown by decreased water content and downregulated AQP4 expression at mRNA and protein levels. RLN-2 reduced oxidative stress markers such as malondialdehyde (MDA) and reactive oxygen species (ROS) and increased the activity of catalase (CAT). Further, RLN-2 mitigated neuroinflammation by reducing the levels of pro-inflammatory cytokines (TNF-α and IL-6) and by inhibiting the activation of M1 microglia while promoting the polarization of M2 microglia. It also inhibited the activation of the NF-κB signaling and strengthened the activation of the STAT6 signaling in the spinal cord of SCI mice. These findings suggest that RLN-2 may be a promising therapeutic agent for the treatment of spinal cord injury.
本研究旨在评估松弛素-2(RLN-2)在促进小鼠脊髓损伤(SCI)后功能恢复和神经保护方面的治疗效果。此外,连续皮下输注Serelaxin(0.5毫克/千克/天;重组人松弛素-2)可改善神经功能恢复,与SCI组相比,Basso-Beattie-Bresnahan(BBB)评分更高,步幅角度减小,这证明了这一点。此外,RLN-2有效减轻了损伤脊髓的水肿,表现为含水量降低以及水通道蛋白4(AQP4)在mRNA和蛋白质水平的表达下调。RLN-2降低了丙二醛(MDA)和活性氧(ROS)等氧化应激标志物的水平,并增加了过氧化氢酶(CAT)的活性。此外,RLN-2通过降低促炎细胞因子(TNF-α和IL-6)的水平以及抑制M1小胶质细胞的激活,同时促进M2小胶质细胞的极化,从而减轻神经炎症。它还抑制了SCI小鼠脊髓中NF-κB信号的激活,并增强了STAT6信号的激活。这些发现表明,RLN-2可能是一种有前途的脊髓损伤治疗药物。