Abstract
The aim of the present study was to investigate the effect of Lidocaine on hypoxia-induced injury in cardiomyoblasts whilst exploring the associated molecular mechanism. In the present study, hypoxia was induced in H9c2 cells to establish an in vitro model of myocardial infarction. The cells were treated with lidocaine (0.5, 1, 5, 10 mM) for 48 h under hypoxic conditions. Cell viability and apoptosis levels were determined by MTT assay and flow cytometry, and ELISA was used to measure the levels of inflammatory cytokines released. A creatine kinase isoenzyme/cardiac troponin I detection kit was used to show that lidocaine significantly reduced hypoxia-induced cardiac troponin 1 and creatine kinase-muscle/brain release in a dose-dependent manner. Mitochondrial viability staining suggested that lidocaine significantly enhanced mitochondrial viability under hypoxic conditions. Lidocaine also significantly reduced hypoxia-induced apoptosis and increased H9c2 viability in a dose-dependent manner. Additionally, under hypoxic conditions, lidocaine dose-dependently promoted Bcl-2 expression, while decreasing Bax and caspase-3 expression in H9c2 cells. ELISA and reverse transcription quantitative PCR were used to detect the levels of tumor necrosis factor (TNF-α), interleukin (IL)-1β and IL-6 released by H9c2 cells. Results showed that lidocaine markedly reduced the hypoxia-induced expression levels of IL-1β, TNF-α and IL-6 in a dose-dependent manner. In addition, protein levels of phosphorylated (p)-ERK1/2 and NF-κB p-p65 were analyzed by western blotting, and results indicated that lidocaine significantly increased the protein levels of p-ERK1/2 and decreased the protein level of NF-κB p-p65 in a dose-dependent manner under hypoxic conditions. These data suggested that lidocaine might protect cardiomyoblasts from hypoxia-induced injury via activation of the mitogen activated protein kinase/ERK/NF-κB signaling pathway.