Modulatory Effects of Butorphanol on Cognitive Function in Postpartum Sleep-Disordered Rats via the TLR4/NF-κB Signaling Pathway

Abstract

Background: Cognitive dysfunction resulting from sleep deprivation has received widespread attention. However, the impact of postpartum sleep disorders (PSD) arising from childbirth-related factors on maternal cognitive function remains unclear. Butorphanol, a potential pharmacological agent, may play a crucial role in improving cognitive function in postpartum sleep disorders. Objective: This study aimed to investigate the impact of butorphanol on cognitive function among rats with postpartum sleep disorders and elucidate the underlying molecular mechanisms. Methods: A PSD rat model was established 24 hours after natural delivery. The rats were divided into three groups: the control group, the model group, and the butorphanol group. Furthermore, neurological function, brain tissue damage, apoptosis rate, expression levels of inflammatory factors, and related signaling pathways were assessed employing Enzyme-Linked Immunosorbent Assay (ELISA), Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), and Western blot analysis. The Morris water maze test was used to evaluate cognitive function in rats. Results: The butorphanol-treated group of rats exhibited significant improvement in sleep, with reduced wakefulness compared to the model group (p < 0.05). In the Morris water maze test, rats in the butorphanol-treated group showed significantly decreased escape latency and increased platform entries (p < 0.05), indicating improved cognitive function after treatment. Furthermore, butorphanol reduced the expression levels of inflammatory factors (Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, and IL-6) by modulating the Toll-Like Receptor 4/Nuclear Factor Kappa B (TLR4/NF-κB) signaling pathway (p < 0.05), thereby exerting anti-inflammatory and anti-apoptotic effects. Conclusion: Butorphanol can enhance cognitive function in postpartum sleep-disordered rats by regulating the TLR4/NF-κB signaling pathway, providing a theoretical basis for its clinical application in treating postpartum sleep disorders.