Exploring the Role of Nrf2 in Alleviating Spinal Cord Injury-Induced Oxidative Stress and Neuronal Apoptosis Based on GAPDH/Siah1 Axis

Background: Spinal cord injury is a condition where the spinal cord is damaged by external trauma or other types of injuries. The spinal cord is part of the central nervous system, located within the spine and responsible for transmitting neural signals to control the body's motor and sensory functions. This study aimed to analyze the mechanism and pathway of nuclear factor erythroid-2-related factor 2 (Nrf2) in spinal cord injury (SCI).Methods: Twenty SD rats were randomized to sham, model, blank, and intervention groups, with a surgical incision made alone in the sham group and an SCI model established in the other three groups. Rats in the intervention group received intramyelin injections of vectors targeted to increase Nrf2 expression, while those in the blank group were injected with corresponding empty vectors. Morris water maze (MWM) tests were carried out on each group of rats, and the escape latency and swimming speed were recorded. Subsequently, the rats were killed to collect the spinal cord tissue for Hematoxylin-Eosin (HE), toluidine blue and Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) staining, as well as the determination of Nrf2 fluorescence intensity using immunofluorescence. Finally, the levels of oxidative stress, inflammatory factors and Glyceraldehyde-3Phosphate Dehydrogenase (GAPDH)/Seven in Absentia Homolog 1 (Siah1) pathway proteins were detected.Results: The Nrf2 fluorescence intensity was higher in the model, blank and intervention groups compared with the sham group (p < 0.05). In the MWM test, the escape latency of the intervention group was lower compared with the model and blank groups, and was higher compared with the sham group, while the swimming speed of the intervention group was lower versus the sham group (p < 0.05). According to spinal cord tissue staining, the model and blank groups had severe nerve injury and a large number of cells apoptosis, which were significantly ameliorated in the intervention group (p < 0.05). Milder oxidative stress and inflammatory reactions in the intervention group were identified compared with the model and blank groups, which were still higher as compared to the sham group (p < 0.05). Finally, the GAPDH/Siah1 axis was found to be activated in the model and blank groups, but it was inhibited in the intervention group (p < 0.05).Conclusion: Upregulation of Nrf2 expression can alleviate the pathological injury of SCI, and its mechanism is related to the inhibition of GAPDH/Siah1 axis.