Effect of High Mobility Group Box-1 Protein on α2A-Adrenoceptors-Mediated Acute Lung Injury in a Rat Model of Sepsis

Objective: To investigate the effect of high mobility group box-1 protein on α2A-adrenaline receptors-mediated acute lung injury in a rat model of sepsis.Methods: In a sepsis model by cecal ligation and puncture(CLP),sixty-four SD rats were randomly divided into the following groups: CLP group and CLP + maleate group.Plasma levels of TNF-α,HMGB1 and IL-10 were determined at the following time points: 2(T1),6(T2),12(T3) and 24 h(T4) after CLP.Lung was removed for the determinations of pulmonary wet-to-dry ratio(W/D),myeloperoxidase activity(MPO),total histological scores and HMGB1 immunohistochemistry analysis 24 h after CLP.Results: Plasma levels of TNF-α at T2 and HMGB1 at T2,T3 and T4 were significantly lower in CLP + maleate group than CLP group(P0.05).There was no difference in IL-10 over time between groups(P0.05).Pulmonary levels of W/D,MPO,total histological scores and HMGB1 expression were significantly lower than those in CLP group(P0.05).Conclusions: HMGB1 plays a key role in the pathophysiology of ALI,and antagonism of α2A-adrenoceptors improves pulmonary function by inhibiting HMGB1.