Expression of Nrf2-Keap1-ARE signal pathway in traumatic lung injury and functional study

OBJECTIVE: Traumatic lung injury (TLI) can cause inflammation and oxidative stress, or even leads to acute respiratory distress syndrome (ARDS) and death. Nuclear factor erythroid-2 related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signal pathway participates in disease occurrence and progression via regulating inflammatory and oxidative stress response, but with its expression and functional roles in TLI largely unknown.

MATERIALS AND METHODS: Wistar rats were randomly divided into control group, TLI group by crushing method, and Nrf2 activation group which received Nrf2 specific agonist sulforaphane 30 min before TLI treatment. Artery blood gas (ABG), wet/dry mass ratio (W/D) of lung tissues, myeloid peroxidase (MPO) and superoxide dismutase (SOD) activity of lung tissue were analyzed. Keap1 and ARE mRNA levels were tested by Real-time PCR, while Nrf2 protein was measured by Western blot. Inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) were quantified by enzyme-linked immunosorbent assay (ELISA).

RESULTS: TLI model had lower ABG or SOD, higher W/D ratio, MPO value, elevated expressions of TNF-α, IL-2, and Keap1, plus decreased Nrf2 and ARE expression (p<0.05). Nrf2 activation significantly improved ABG, decreased W/D ratio and MPO value, enhanced SOD activity, decreased TNF-α and IL-2 secretion, suppressed Keap1 expression, and facilitated Nrf2 and ARE expressions (p<0.05).

CONCLUSIONS: Nrf2-Keap1-ARE signal pathway can improve TLI-related pathology via modulating oxidative stress response and suppressing inflammation.

L'articolo Expression of Nrf2-Keap1-ARE signal pathway in traumatic lung injury and functional study sembra essere il primo su European Review.

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