Abstract
MicroRNA‑126 (miR‑126) has been reported to be implicated in the pathogenesis of cerebral ischemia/reperfusion (I/R) injury; however, its role is still unclear and requires further investigation. The objective of the present study was to determine the neuroprotective effect of miR‑126 overexpression against oxygen‑glucose deprivation/reoxygenation (OGD/R)‑induced human umbilical vein endothelial cell (HUVEC) injury, an in vitro model of cerebral I/R injury, and to further explore the role of the NAD‑dependent protein deacetylase sirtuin‑1 (SIRT1)/nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling pathway in this process. The results of the present study revealed that miR‑126 expression was markedly reduced in HUVECs subjected to OGD/R treatment. Functional experiments demonstrated that transfection with miR‑126 mimics attenuated OGD/R‑induced down‑regulation of cell viability, and reversed OGD/R‑induced up‑regulation of lactate dehydrogenase release, apoptosis and caspase‑3 activity in HUVECs. Notably, OGD/R reduced SIRT1 and heme oxygenase‑1 expression, and induced the nuclear translocation of Nrf2, as demonstrated by the increase in cytoplasmic Nrf2 expression and the decrease in nuclear Nrf2 expression. Following transfection with miR‑126 mimics, these effects of OGD/R were reversed, indicating that miR‑126 overexpression promoted the SIRT1/Nrf2 signaling pathway. Additionally, miR‑126 mimics attenuated OGD/R‑induced cytotoxicity and apoptosis, which was blocked by inhibition of the SIRT1/Nrf2 signaling pathway followed by transfection with SIRT1‑small interfering RNA (siRNA). Furthermore, miR‑126 mimics decreased ROS generation and malondialdehyde content, and increased superoxide dismutase and glutathione peroxidase activity in HUVECs exposed to OGD/R, and these effects of miR‑126 mimics were also blocked by SIRT1‑siRNA. Additionally, the miR‑126 mimics‑induced the decreases in the levels of pro‑inflammatory cytokines, including tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6, and the miR‑126 mimics‑induced increase in anti‑inflammatory cytokines, including IL‑10, were reversed by SIRT1‑siRNA. Overall, these results suggested that miR‑126 overexpression attenuated OGD/R‑induced neurotoxicity to HUVECs by alleviating oxidative stress and the inflammatory response via promotion of the SIRT1/Nrf2 signaling pathway.