Apoptosis is a cellular mechanism contributing to cardiac surgery using cardiopulmonary bypass (CPB)-induced lung injury. The ubiquitous PI3K/Akt pathway regulates proliferation, apoptosis and differentiation by controlling a broad range of target proteins including NF-κB and GSK-3β. The roles of the PI3K/Akt/NF-κB and PI3K/Akt/GSK-3β pathways in CPB-related lung injury are unclear.

Seventy-two male Sprague-Dawley rats were assigned into sham, CPB, Wortmannin (Wtn) and insulin-like growth factor-I (IGF-I) groups (n = 18, each). Six subjects per group were evaluated at each of three time points: Prior to CPB (T1); opening of the left hilus pulmonis (T2); and 90 min after CPB (T3). Arterial blood specimens were obtained at each time point to test respiratory and oxygenation indices. Left lung tissues were processed for H&E and TUNEL staining. Western blot was employed to evaluate protein levels and activities of Akt, phospho-Akt (p-Akt), GSK-3β, phospho-GSK-3β (p-GSK-3β) and nuclear NF-κB.

Lung ischemia/reperfusion and CPB caused notable lung injury, as evidenced by lung functional decline and pathological deterioration, accompanied by increases in apoptosis and expression levels of p-Akt, p-GSK-3β and nuclear NF-κB in lungs (all P < 0.05 vs. Sham). At T3, Wtn-treated CPB subjects showed worsened lung function and pathological lung structures, as well as apoptosis in lungs (all P < 0.05 vs. CPB); additionally, Wtn inhibited Akt phosphorylation and slightly, but significantly increased expression of nuclear NF-κB (both P < 0.001 vs. CPB). Conversely, treatment of subjects with IGF-I increased Akt phosphorylation (P < 0.001 vs. CPB), inhibited expression of nuclear NF-κB (P = 0.008 vs. CPB), improved lung function and tissue morphology (both P < 0.05 vs. CPB), and reduced apoptosis in lungs (P < 0.001 vs. CPB). Neither Wtn nor IGF-I did alter GSK-3β phosphorylation levels (P =  0.836 and P =  0.669 vs. CPB, respectively).

The PI3K/Akt/NF-κB pathway played a role in CPB-related lung injury, possibly through mediating apoptosis in lungs. GSK-3β, a signaling effector that also participated in CPB-induced apoptosis in lungs, but was not regulated by the PI3K/Akt pathway in this context.