Abstract: The purpose of this study was to investigate the relationship between the edaravone protective effects on neurons and Nrf2 signaling molecules in cerebral ischemia-reperfusion injury. In vivo experiments were performed by establishing a middle cerebral artery occlusion model in SD rats, and in vitro experiments were performed using hydrogen peroxide (H2O2) to damage PC12 cells to establish an oxidative stress model. The pathological status of the brain was detected by TTC, HE and Nissl staining. Reactive oxygen species (ROS), malondialdehyde (MDA) contents, and superoxide dismutase (SOD) activity were measured to reflect the level of oxidative stress. In addition, Hoechst 33342 staining and measurement of mitochondrial membrane potential (MTP) were used to investigate the cell-level damage. Nrf2 expression was determined using immunohistochemistry and Western blotting. Nrf2 knockout PC12 cells were constructed to confirm the role of Nrf2 signaling molecules in inhibiting oxidative stress-induced injury. The results suggest that after edaravone administration, both animal-level and TTC staining confirmed that cerebral ischemia-reperfusion injury (CIRI) rats had reduced cerebral infarcted areas (P <0.001), ROS and MDA levels decreased (P<0.01), SOD activity increased (P<0.01); at the cell level, apoptotic cells decreased (P<0.05), MTP increased (P<0.01), ROS and MDA levels decreased, and the SOD activity increased (P <0.01); at the molecular level, immunohistochemistry and Western blotting showed that the Nrf2 protein level was increased compared with the control group. H2O2 induced damage in Nrf2-knockout PC12 cell was aggravated and the therapeutic effect of edaravone was significantly weakened. In summary, Nrf2 plays a key role in edaravone in reducing cerebral ischemia-reperfusion-induced oxidative stress injury.
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