PURPOSE: To investigate the effects of α2A-adrenoreceptor blockade on acute lung injury (ALI) and high mobility group box-1 protein (HMGB1) expression in a rat model of sepsis. METHODS: Sepsis was induced in male rats by cecal ligation and puncture (CLP). Thirty adult male Sprague-Dawley rats were equally randomized to the Sham group, the CLP group, and the CLP+maleate group. Five hours after CLP, rats received an intraperitoneal injection of BRL-44408 maleate or the same volume of vehicle. Serum levels of TNF-α, IL-6, IL-10, HMGB1, and norepinephrine were measured at baseline, 6, 18, and 24h after CLP. Lung TNF-α, IL-6, IL-10, immunohistochemical and western blotting analysis of HMGB1, nuclear factor (NF)-κB activation, myeloperoxidase (MPO) activity, histological scores, and wet-to-dry weight ratio were determined 24h after CLP. In additional CLP and CLP+maleate groups, the 7 day survival rate was evaluated. RESULTS: Compared with the CLP group, serum TNF-α at 6h, HMGB1 at 18 and 24h, and norepinephrine at 6 and 18 h after CLP decreased in the CLP+maleate group. Lung TNF-α, IL-6, and HMGB1 expressions decreased at 24h after CLP. NF-κB activation, MPO activity, histological scores, and wet-to-dry weight ratio were lower in the CLP+maleate group than the CLP group. There was no significant difference in 7 day survival rate between the CLP and CLP+maleate groups. CONCLUSIONS: The α2A-adrenoreceptor blockade by a specific antagonist maleate improves sepsis-induced acute lung injury accompanied with depressed HMGB1 expression in rats. The mechanism seemed to be mediated partly through downregulation of the signal transductions of the NF-κB pathway.
PURPOSE: To investigate the effects of α2A-adrenoreceptor blockade on acute lung injury (ALI) and high mobility group box-1 protein (HMGB1) expression in a rat model of sepsis. METHODS:Sepsis was induced in male rats by cecal ligation and puncture (CLP). Thirty adult male Sprague-Dawley rats were equally randomized to the Sham group, the CLP group, and the CLP+maleate group. Five hours after CLP, rats received an intraperitoneal injection of BRL-44408 maleate or the same volume of vehicle. Serum levels of TNF-α, IL-6, IL-10, HMGB1, and norepinephrine were measured at baseline, 6, 18, and 24h after CLP. Lung TNF-α, IL-6, IL-10, immunohistochemical and western blotting analysis of HMGB1, nuclear factor (NF)-κB activation, myeloperoxidase (MPO) activity, histological scores, and wet-to-dry weight ratio were determined 24h after CLP. In additional CLP and CLP+maleate groups, the 7 day survival rate was evaluated. RESULTS: Compared with the CLP group, serum TNF-α at 6h, HMGB1 at 18 and 24h, and norepinephrine at 6 and 18 h after CLP decreased in the CLP+maleate group. Lung TNF-α, IL-6, and HMGB1 expressions decreased at 24h after CLP. NF-κB activation, MPO activity, histological scores, and wet-to-dry weight ratio were lower in the CLP+maleate group than the CLP group. There was no significant difference in 7 day survival rate between the CLP and CLP+maleate groups. CONCLUSIONS: The α2A-adrenoreceptor blockade by a specific antagonist maleate improves sepsis-induced acute lung injury accompanied with depressedHMGB1 expression in rats. The mechanism seemed to be mediated partly through downregulation of the signal transductions of the NF-κB pathway.
Authors: Laurival A De Luca; Roberto L Almeida; Richard B David; Patricia M de Paula; Carina A F Andrade; José V Menani Journal: J Physiol Date: 2015-07-07 Impact factor: 5.182