Background: Cu/Zn-SOD plays a crucial role in uremia combined with cerebral hemorrhage (UCH). However, its specific role and underlying mechanisms in this condition have not been fully elucidated. This study aims to investigate the effects of Cu/Zn-SOD on uremia-associated cerebral hemorrhage and whether the NF-κB pathway is involved.

Methods: Samples were collected from healthy adult subjects and age-matched patients with uremic cerebral hemorrhage, and a UCH mouse model was established. Western blot and RT-qPCR analyses were used to evaluate the levels of Cu/Zn-SOD, apoptosis-related proteins, inflammatory cytokines, oxidative stress markers, and proteins involved in the NF-κB pathway in UCH patients. The brain water content measurement, ELISA, TUNEL, immunofluorescence, and DCFH-DA assays were also performed to assess brain edema, apoptosis, inflammation, and oxidative stress in UCH brain tissue.

Results: Cu/Zn-SOD expression was significantly downregulated in the human serum of UCH patients (p < 0.001). Overexpression (OE) of Cu/Zn-SOD alleviated brain edema and inhibited cellular apoptosis in mice (p < 0.05), which was reversed by RNAi (p < 0.05). Furthermore, OE reduced inflammation and oxidative stress levels in UCH mice (p < 0.05), which was reversed by RNAi (p < 0.05). Notably, OE suppressed the expression of NF-κB pathway proteins (p < 0.001), while the NF-κB agonist reversed the inhibitory effect of OE on NF-κB (p < 0.001).

Conclusions: Overexpression of Cu/Zn-SOD alleviates the occurrence of UCH by inhibiting the NF-κB pathway, thereby providing a theoretical reference for Cu/Zn-SOD as a potential target for the prevention and treatment of UCH.