| Popis: |
Background Persistent immunosuppression characterized by immune cells apoptosis and T- lymphocyte subsets imbalance, occurs in septic patients with poor outcomes. Recent studies reported that Esmolol improved survival in septic shock via modulating immune responses. We hypothesized Esmolol alleviate sepsis-induced immunosuppression by regulating immune cell apoptosis and differentiation and sought to investigate the potential mechanisms and optimal dose. Methods Four hours after cecal ligation and puncture (CLP), Wistar rats were randomized into CLP, CLP + E-5 (Esmolol:5mg.kg− 1.h− 1) and CLP + E-18 (Esmolol:18mg.kg− 1.h− 1) group. Another 8 rats were under sham operation. 18 hours after CLP, hemodynamics and organ histological injuries were evaluated, peripheral blood mononuclear cells apoptosis and circulating T-lymphocyte subsets counts were determined by flow cytometry, protein expressions of p-Akt, Bcl-2, cleaved Caspase-3 and p-Erk1/2 were determined by western blot and immunohistochemistry. mRNA and protein expressions of β1-adrenoreceptors were evaluated by quantitative real-time PCR and immunohistochemistry. Results CLP induced tachycardia, hypotension, hyperlactatemia and multiple organ injuries. Infusion of Esmolol at 5mg.kg− 1.h− 1 didn't reduce heart rate, but improved mean arterial pressure, lactatemia and multiple organ injuries, decreased circulating T-lymphocyte apoptosis and the ratio of T help 2 cells and T help 1 cells, unregulated p-Akt and Bcl-2 expression and down-regulated cleaved Caspase-3 and p-Erk1/2 expression. Conclusions Esmolol without heart rate reduction attenuated sepsis-induced immunosuppression by preventing T-lymphocytes from apoptosis through regulating Akt/Bcl-2/Caspase-3 pathway and reducing naive CD4+ T cells differentiation to T help 2 cell through inhibiting Erk1/2 activation. Esmolol may be a potential immune regulator in septic shock. |
