Wu Weidong, Wei Ningxian, Wang Lihui, Kong Danhui, Shao Gang, Qin Yingchun, Wang Lixin, Du Yansheng
Danyang People's Hospital of Jiangsu Province, Danyang, Jiangsu, PR China.
School of Medicine, Southeast University, Nanjing, Jiangsu, PR China.
Oncotarget. 2017 Sep 21;8(50):87658-87666. doi: 10.18632/oncotarget.21142. eCollection 2017 Oct 20.
Acute traumatic spinal cord injury (tSCI) results in a lifetime of paralysis associated with a host of medical complications. The developing secondary complications of tSCI may result in further chronic neurodegenerative diseases. Sevoflurane preconditioning (SF-PreCon) has shown guaranteed protective effects in myocardial or cerebral ischemic/reperfusion injury. However, the role of SF-PreCon in tSCI still remains to be elucidated. Here, we found that SF-PreCon ameliorated the developing secondary complications through reducing the apoptosis rate and the secretion of inflammatory cytokines in injured spinal cord tissues, and therefore enhancing the recovery after tSCI. Notably, we demonstrated that SF-PreCon ameliorates tSCI through inhibiting Cycloxygenase-2 (COX-2). Importantly, we verified that SF-PreCon inhibits the expression of COX-2 and reduces the apoptosis rate after tSCI via the induction of Caveolin-3 (Cav-3). Taken together, our results suggest that SF-PreCon ameliorates tSCI via Cav-3-dependent COX-2 inhibition and provide an economical and practical method against the secondary injury after tSCI.
急性创伤性脊髓损伤(tSCI)会导致终身瘫痪,并伴有一系列医学并发症。tSCI不断发展的继发性并发症可能会导致进一步的慢性神经退行性疾病。七氟醚预处理(SF-PreCon)已在心肌或脑缺血/再灌注损伤中显示出可靠的保护作用。然而,SF-PreCon在tSCI中的作用仍有待阐明。在此,我们发现SF-PreCon通过降低损伤脊髓组织中的凋亡率和炎性细胞因子的分泌来改善不断发展的继发性并发症,从而促进tSCI后的恢复。值得注意的是,我们证明SF-PreCon通过抑制环氧化酶-2(COX-2)来改善tSCI。重要的是,我们证实SF-PreCon通过诱导小窝蛋白-3(Cav-3)来抑制COX-2的表达并降低tSCI后的凋亡率。综上所述,我们的结果表明SF-PreCon通过依赖Cav-3的COX-2抑制来改善tSCI,并提供了一种针对tSCI后继发性损伤的经济实用方法。