Sirtuin-1和Wnt/β-Catenin信号通路在大鼠脊髓损伤模型中的作用,Computational and Mathematical Methods in Medicine

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Sirtuin-1和Wnt/β-Catenin信号通路在大鼠脊髓损伤模型中的作用
Computational and Mathematical Methods in Medicine Pub Date : 2022-03-27 , DOI: 10.1155/2022/1799607
Kunming Zhu ₁ , Weiwei Xu ₂ , Donghe Han ₃ , Xifan Mei ₁

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Sirtuin-1 (SIRT1) 具有抗炎和抗氧化作用，据报道与脊髓损伤 (SCI) 有关。Wnt/ β -catenin信号已被证明在慢性疾病的发病机制中发挥着关键作用，并参与SCI后神经功能的恢复。但SCI中它们之间的具体联系尚不清楚。此外，针对创伤后星形胶质细胞凋亡对于改善神经变性和运动功能至关重要。因此，在本文中，我们在SCI大鼠模型和过氧化氢（H ₂ O _{2处理的原代星形胶质细胞）中研究了}β -catenin和SIRT1的关系。）或氯化锂（LiCl）。结果显示，SCI后，SCI面积和运动功能随时间恢复，β -catenin逐渐升高至第7天，然后依次下降，直至第4周，与细胞凋亡呈正相关。SIRT1及其下游FOXO4的表达量逐渐升高，且β -catenin与SIRT1的表达量呈负相关。此外，在原代培养的星形胶质细胞中用H ₂ O _{2处理显着增加了}β-catenin和Caspase-3表达，同时SIRT1和Forkhead box O-(FOXO-)4表达减少。免疫荧光结果与此一致。LiCl的施用进一步加剧了上述结果。这些结果提示，SCI中SIRT1与β -catenin呈负相关，促进运动神经元细胞凋亡，这可能与FOXO4的参与有关。

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Effect of Sirtuin-1 and Wnt/β-Catenin Signaling Pathway in Rat Model of Spinal Cord Injury

Sirtuin-1 (SIRT1) has anti-inflammatory and antioxidant effects and has been reported to be involved in spinal cord injury (SCI). Wnt/β-catenin signal has been shown to play a critical role in the pathogenesis of chronic diseases, and it participated in the recovery of nerve function after SCI. However, the specific link between them in SCI is unclear. In addition, targeting posttraumatic astrocyte apoptosis is crucial for improving neural degeneration and locomotor function. Therefore, in this article, we studied the relationship of β-catenin and SIRT1 using in the SCI rat model and primary astrocyte treated with hydrogen peroxide (H₂O₂) or lithium chloride (LiCl). Results showed that after SCI, SCI area and motor function recover over time, and β-catenin is gradually increased to the seventh day and then in turn decreases until 4 weeks, positively correlated with cell apoptosis. The expression of SIRT1 and downstream FOXO4 gradually increased, and β-catenin is negatively correlated with SIRT1 expression. Moreover, treatment with H₂O₂ in primary cultured astrocyte significantly increased β-catenin and Caspase-3 expression, while decreased SIRT1 and Forkhead box O- (FOXO-) 4. The immunofluorescence results are consistent with this. Administration of LiCl further aggravates the above results. These findings suggest that SIRT1 is negatively correlated with β-catenin in SCI, which promotes the apoptosis of motor neuron cells, which may be related to the participation of FOXO4.

更新日期：2022-03-27

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