Dexmedetomidine Ameliorates Post-CPB Lung Injury in Rats by Activating the PI3K/Akt Pathway

Abstract

Purpose: To investigate the protective effects of dexmedetomidine (Dex) on post cardiopulmonary bypass (CPB) lung injury in rats and to explore the possibility of underlying mechanisms involving phosphatidylinositol 3-kinase (PI3K)/Akt. Materials and Methods: Forty healthy male Sprague–Dawley rats were randomly divided into five groups (n = 8 for each). A left lung ischemia-reperfusion injury model of CPB was established in all five groups. Rats were given saline, dexmedetomidine (Dex), dimethyl sulfoxide (DMSO), wortmannin (Wtm), and Dex plus Wtm during the CPB process, in Group Saline, Dex, DMSO, Wtm, and Dex + Wtm, respectively. Mean arterial pressure, oxygenation index (OI), and respiratory index (RI) were measured at the following three timepoints: before CPB (T1), at the onset of opening of the left hilus pulmonis (T2), and at the end of the CPB process (T3). At T3, hematoxylin and eosin (H&E) staining was conducted to evaluate pathology of lung injury. The rate of lung tissue apoptosis was determined by flow-cytometry. The expression of Akt, p-Akt, caspase-3, and caspase-9 was assessed by Western blot. Results: Dex treatment during CPB protected rat lungs from post-CPB lung injury, manifested by improved lung function, mitigated pathological damage, and reduced lung tissue apoptosis. The expression and phosphorylation of Akt was significantly enhanced by Dex treatment compared to the saline/DMSO-treated group. Wtm, a recognized PI3K inhibitor, abolished the protective effect of Dex. The levels of caspase-3 and caspase-9 were also significantly elevated in the Wtm-treated group. Conclusions: Dex reduces post-CPB lung injury in rats, at least partially, by activating the PI3K/Akt pathway and inhibiting lung tissue apoptosis.