Original scientific paper
https://doi.org/10.18054/pb.v127i3-4.36145
SIRT2 inhibition: A novel approach to modulateTLR4/NF-κB and Nrf2 pathways in post-ICH neuroprotection
Mang Zhu
; Department of Neurosurgery, Xi'an No. 3 Hospital, The Affiliated Hospital of Northwest University, Xi'an, Shaanxi Province, China
Yuan Fang
; Department of Neurosurgery, Xi'an No. 3 Hospital, The Affiliated Hospital of Northwest University, Xi'an, Shaanxi Province, China
*
* Corresponding author.
Abstract
Background and purpose: Intracerebral hemorrhage (ICH) is a severe form of stroke associated with high morbidity and mortality. Secondary injury mechanisms, including neuroinflammation and oxidative stress, exacerbate neuronal damage. SIRT2, a NAD+-dependent deacetylase, is implicated in inflammatory and antioxidant responses. This study investigates the role of SIRT2 inhibition in modulating the TLR4/NF-κB inflammatory pathway and the Nrf2 antioxidant pathway in an in vitro post-ICH model.
Materials and methods: SH-SY5Y neuronal cells were exposed to lipopolysaccharide (LPS) to induce inflammation and hydrogen peroxide (H₂O₂) to simulate oxidative stress. AGK2, a selective SIRT2 inhibitor, was used to assess its effects on these pathways. Western blotting analyzed the expression of SIRT2, TLR4, NF-κB, Nrf2, HO-1, and NQO1, while realtime PCR quantified antioxidant (HO-1, NQO1) and pro-inflammatory cytokine (TNF-α, IL-6) gene expression.
Results: SIRT2 inhibition significantly reduced TLR4 and NF-κB expression while promoting Nrf2 activation and antioxidant gene upregulation. The combination of H₂O₂ and LPS increased pro-inflammatory cytokines, but SIRT2 inhibition mitigated this response, indicating its regulatory role in inflammation and oxidative stress.
Conclusions: SIRT2 inhibition effectively modulates inflammatory and antioxidant responses in an in vitro post-ICH model. Targeting SIRT2 may represent a potential therapeutic approach to mitigate secondary brain injury in ICH by balancing neuroinflammatory and oxidative stress pathways. Further studies are needed to explore its clinical relevance in hemorrhagic stroke.
Keywords
intracerebral hemorrhage; SIRT2; inflammation; oxidative stress; TLR4; NF-κB; Nrf2; HO-1; NQO1; stroke therapy
Hrčak ID:
347132
URI
Publication date:
13.5.2026.
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