The bone marrow mononuclear cells reduce the oxidative stress of cerebral infarction through PI3K/AKT/NRF2 signaling pathway

OBJECTIVE: To evaluate the mechanism of bone marrow mononuclear cells (BMMNCs) in reducing the oxidative stress after cerebral infarction through PI3K/AKT/NRF2 signaling pathway.

MATERIALS AND METHODS: 96 healthy SD rats, which were 6-8-week old, weighting about 250-280 g, were selected for the study. The middle cerebral artery occlusion model (MCAO) was established in SD rats using the suture method. The rats were randomly divided into sham operation group, model group, BMMNCs group and PI3K inhibitor group. 24 rats in each group were selected. 200 μl phosphate-buffered saline (PBS) solution was injected into the caudal vein of the rats in the model group, 200 μl PBS solution containing 5×106 BMMNCs that obtained by gradient centrifugation was injected into the rats in the BMMNCs group, meanwhile, in the PI3K inhibitor group, LY294002 (10 mmol/L/kg) was injected into the lateral ventricle of the brain. After the 3d, 7d and 14d, the modified neurological severity scores (mNSS) were used to evaluate the neurological function. The volume of cerebral infarction was assessed by TTC staining, the VEGF, BDNF, TNF-α, IL-1β, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were detected by ELISA.

RESULTS: The mNSS and the volume of cerebral infarction of the model group were significantly higher than those of the sham operation group (p<0.05), while the mNSS and the volume of cerebral infarction of the BMMNCs group were lower than those of the model group, higher than those of the sham operation group (p<0.05). The VEGF, BDNF, TNF-α, IL-1β, MDA, SOD and GSH-Px levels of the model group were significantly higher than those of the sham operation group (p<0.05).

CONCLUSIONS: BMMNCs can reduce the oxidative stress, apoptosis, and inflammatory reaction through PI3K/AKT/NRF2 signaling pathway, thus promoting the secretion of nerve and vascular cytokines, improving the neurological function and reducing the infarct scope.

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