Sirtuin1 modulates P53/Nrf2 pathway to promote spinal cord injury repair

Spinal cord injury (SCI) is characterized by its high incidence, high disability rate, and high treatment costs, making the development of effective therapeutic strategies a major focus. Secondary injury mechanisms in SCI involve complex processes such as inflammation, oxidative stress, and apoptosis, which are critical to patient prognosis.

This study investigates the role of SIRT1 in SCI repair, particularly its molecular mechanisms in regulating the P53/Nrf2 signaling pathway. By constructing a recombinant adenovirus overexpressing SIRT1 and conducting both in vitro and in vivo validation, we found that SIRT1 modulates the P53/Nrf2 pathway by downregulating P53 and upregulating Nrf2 expression, significantly inhibiting the expression of inflammatory factors TNF-α, IL-1β, and IL-6, while increasing the expression of the anti-inflammatory factor IL-10. Additionally, SIRT1 reduced apoptosis by regulating Bax and Bcl-2 expression, and enhanced cellular antioxidant capacity through activation of Nrf2. These regulatory effects significantly promoted motor function recovery in SCI rats.

This study provides mechanistic evidence for the neuroprotective role of SIRT1 in SCI and establishes a foundation for considering SIRT1 as a novel therapeutic target for SCI.