Abstract
Lidocaine, a local anesthetic, is a valuable agent for the treatment of neuronal ischemia/reperfusion (I/R) injury. The aim of the present study was to investigate the role of lidocaine in oxygen-glucose deprivation/reperfusion (OGD/R)-induced cortical neurons and explore the related molecular mechanisms. Cerebral cortical neurons were isolated from Sprague-Dawley rat embryos and stimulated with OGD/R to establish an in vitro I/R injury model. Subsequently, neuronal cell viability, cytotoxicity and apoptosis were evaluated by performing the MTT assay, lactate dehydrogenase (LDH) assay and flow cytometry, respectively. The results suggested that OGD/R exposure significantly decreased cerebral cortical neuron cell viability, accelerated LDH release and induced cell apoptosis compared with control neurons, indicating that cerebral I/R injury was stimulated by OGD/R treatment. Further investigation indicated that 10 µM lidocaine significantly enhanced neuronal cell viability, and reduced LDH release and neuronal cell apoptosis in OGD/R-exposed cells compared with the OGD/R + saline group, which indicated that lidocaine displayed neuroprotective effects against I/R damage. In addition, the findings of the present study suggested that OGD/R exposure significantly decreased Bcl-2 and Bcl-xl protein expression levels, but increased Bax protein expression levels, the Bax/Bcl-2 ratio and caspase-3 activity compared with control neurons. However, lidocaine reversed OGD/R-mediated alterations to apoptosis-related protein expression. Furthermore, the results of the present study indicated that lidocaine increased Wnt3a, β-catenin and cyclin D1 expression levels in OGD/R-exposed cells compared with the OGD/R + saline group, thus activating the Wnt/β-catenin signaling pathway. The findings of the present study suggested that lidocaine served a protective role in OGD/R-triggered neuronal damage by activating the Wnt/β-catenin signaling pathway; therefore, lidocaine may serve as a potential candidate for the treatment of cerebral I/R injury.