Degenerative cervical myelopathy (DCM) is one of the most common and serious neurological diseases. Cilostazol has protective effects of anterior horn motor neurons and prevented the cell apoptosis. However, there was no literatures of Cilostazol on DCM. In this study, we established the DCM rat model to detect the effects of Cilostazol. Meanwhile, the neurobehavioral assessments, histopathology changes, inflammatory cytokines, Thioredoxin-interacting protein (TXNIP), NOD‑like receptor pyrin domain containing 3 (NLRP3) and pro-caspase-1 expressions were detected by Basso, Beattie, and Bresnahan score assessment, Hematoxylin and Eosin Staining, Enzyme-linked immunosorbent assay, immunofluorescence and Western blotting, respectively. After treated with Cilostazol, the Basso, Beattie, and Bresnahan (BBB) score, inclined plane test and forelimb grip strength in DCM rats were significantly increased meanwhile the histopathology injury and inflammatory cytokines were decreased. Additionally, TXNIP, NLRP3 and pro-caspase-1 expressions levels were decreased in Cilostazol treated DCM rats. Interestingly, the using of siTXNIP significantly changed inflammatory cytokines, TXNIP, NLRP3 and pro-caspase-1 expressions, however there was no significance between siTXNIP and Cilostazol + siTXNIP group. These observations showed that Cilostazol rescues DCM injury and ameliorates neuronal destruction mediated by TXNIP/NLRP3/caspase-1 and pro-inflammatory cytokines. As a result of our study, these findings provide further evidence that Cilostazol may represent promising therapeutic candidates for DCM.

中文翻译：

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西洛他唑通过 TXNIP-NLRP3 通路预防退行性脊髓型颈椎病损伤和细胞焦亡

退行性脊髓型颈椎病（DCM）是最常见、最严重的神经系统疾病之一。西洛他唑对前角运动神经元具有保护作用，防止细胞凋亡。但目前尚无西洛他唑治疗DCM的文献。在本研究中，我们建立了DCM大鼠模型来检测西洛他唑的作用。同时，通过Basso、Beattie和Bresnahan评分评估检测神经行为评估、组织病理学变化、炎症细胞因子、硫氧还蛋白相互作用蛋白（TXNIP）、NOD样受体pyrin结构域3（NLRP3）和pro-caspase-1表达。分别进行苏木精和曙红染色、酶联免疫吸附测定、免疫荧光和蛋白质印迹。西洛他唑治疗后，DCM大鼠的Basso、Beattie和Bresnahan（BBB）评分、斜面测试和前肢握力显着增加，同时组织病理学损伤和炎症细胞因子减少。此外，西洛他唑治疗的 DCM 大鼠中 TXNIP、NLRP3 和 pro-caspase-1 表达水平降低。有趣的是，使用siTXNIP显着改变了炎症细胞因子、TXNIP、NLRP3和pro-caspase-1的表达，但siTXNIP和西洛他唑+siTXNIP组之间没有显着性差异。这些观察结果表明，西洛他唑可挽救 DCM 损伤并改善 TXNIP/NLRP3/caspase-1 和促炎细胞因子介导的神经元破坏。我们的研究结果表明，这些发现进一步证明西洛他唑可能是 DCM 的有前景的治疗候选药物。