Resveratrol Regulates Cellular Activity through the PI3K/AKT Signaling Pathway Involved in Spinal Cord Injury

Abstract

Backgrounds: The incidence of spinal cord injury (SCI) is progressively increasing. The persistent SCI often leads to paralysis, emphasizing the need for timely and effective treatment. In this study, we analyzed the effect of resveratrol (Res) in ameliorating SCI and its effect on astrocytes, aiming to provide new clinical insights for treating SCI in the future. Methods: Sprague-Dawley (SD) rats (n = 25) were divided into sham (sham operation), SCI (SCI modeling), Res (SCI modeling+intraperitoneal Res injection), adenosine triphosphate (ATP; SCI modeling+intraperitoneal injection of exogenous ATP), and Res+ATP (SCI modeling+intraperitoneal injection of Res and ATP) groups. Inflammation, oxidative stress, and apoptosis were assessed in the spinal cord tissue obtained from each group. Astrocytes were purchased, and an SCI model was induced through hypoxia/reoxygenation to observe the effect of Res on cell viability. Moreover, the expression levels of the Phosphatidylinositol3-kinase (PI3K)/Protein kinase B (AKT) pathway were determined in rats and cells. Results: The SCI group exhibited severe pathological injury, intensified tissue inflammatory and oxidative stress responses, and increased apoptosis rate (p < 0.05). Moreover, pathological injuries were alleviated in Res and ATP groups (p < 0.05), with no significant inter-group difference (p > 0.05). The Res+ATP group showed better SCI repair effects than the Res and ATP groups (p < 0.05). Furthermore, in cell-based experiments, cell activation was lower in the SCI group than in the sham group (p < 0.05). The improving capability was higher in the Res and ATP groups than in the SCI group (p < 0.05). The Res+ATP group exhibited astrocyte activation and axonal regeneration ability second only to the sham group (p < 0.05). Moreover, the PI3K/AKT pathway was inhibited in both rats and cells in the SCI group, while p-PI3K/PI3K and p-AKT/AKT levels were increased in Res, ATP, and Res+ATP groups (p < 0.05). Conclusion: Res can repair the pathological injury in SCI by activating the PI3K/AKT axis, and promote astrocyte activation and axonal regeneration.