Liraglutide Activates the Nrf2/HO-1 Antioxidant Pathway and Protects Brain Nerve Cells against Cerebral Ischemia in Diabetic Rats

AbstractThis study aimed to determine the effect of liraglutide pretreatment and to elucidate the mechanism of nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) signaling after focal cerebral ischemia injury in diabetic rats model. Adult male Sprague-Dawley rats were randomly divided into the sham-operated (S) group, diabetes mellitus ischemia (DM + MCAO) group, liraglutide pretreatment normal blood glucose ischemia (NDM+MCAO+L) group, and liraglutide pretreatment diabetes ischemia (DM + MCAO + L) group. At 48 h after middle cerebral artery occlusion (MCAO), neurological deficits and infarct volume of brain were measured. Oxidative stress brain tissue was determined by superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. The expression levels of Nrf2 and HO-1 of brain tissue were analyzed by western blotting. In the DM + MCAO + L group, neurological deficits scores and cerebral infarct volume seemed to decrease at 48 h after MCAO cerebral ischemia compared with those in DM + MCAO group (P<0.05). In addition, the expression of Nrf2 and HO-1 increased in 48 h at liraglutide pretreatment groups after MCAO cerebral ischemia if compared with those in the DM + MCAO group (P<0.05). Furthermore, the DM + MCAO + L group has no significant difference compared with the NDM + MCAO + L group (P>0.05). To sum up, alleviating effects of liraglutide on diabetes complicated with cerebral ischemia injury rats would be related to Nrf2/HO-1 signaling pathway.