Oxidative stress alleviated DL-3-n-Butylphthalide against chronic intermittent hypoxia-induced cognitive deficit by regulating Nrf-2/HO-1 Pathway

Oxidative stress induced by intermittent hypoxia is the main mechanism of cognitive deficit in obstructive sleep apnea (OSA). The Nrf-2/HO-1 signaling pathway is the most important protective signaling pathway for enhancing the antioxidant function of the body and has been reported to play an antioxidant role in cognitive dysfunction in mice with intermittent hypoxia. Clinical studies have preliminarily confirmed that DL-3-n-Butylphthalide (NBP) has a strong antioxidant effect and a neuroprotection for patients with OSA, but its mechanism remains unclear. This study investigated the effects and mechanisms of NBP intervention on learning and memory in 4-week-old male Wistar rats with chronic intermittent hypoxia, which had been subjected to chronic intermittent hypoxia for 6 weeks and injected intraperitoneally with NBP. We found that NBP activated the Nrf-2/HO-1 antioxidant signaling pathway in hippocampus of rats with chronic intermittent hypoxia, reduced MDA, increased SOD levels, inhibited apoptosis, and ultimately improved learning and memory impairment. Therefore, NBP may improve cognitive deficit in OSA patients by activating the Nrf-2/HO-1 antioxidant signaling pathway, inhibiting oxidative stress, and thus reducing apoptosis.