Breviscapine restores sevoflurane-induced cognitive dysfunction by activating the PI3K/Akt pathway and inhibiting NF-κB
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Keywords
cognitive dysfunction, breviscapine, sevoflurane, PI3K/Akt pathway, NF-κB pathway
Abstract
Postoperative cognitive dysfunction (POCD) is featured by cognitive impairments in patients with high morbidity and mortality. Sevoflurane (SEV) is one of the main drugs used to maintain clinical general anesthesia and has been found to cause cognitive dysfunction. Breviscapine has various pharmacological effects. However, the effects of breviscapine on sevoflurane-induced cognitive dysfunction is unclear. The sevoflurane-induced cognitive dysfunction rat model was established. Morris water maze task was conducted to detect time in target quadrant, number of platform crossings, and the distance covered in the quadrant. Hematoxylin and eosin (H&E) staining was used to examine cell morphology. Cell apoptosis was analyzed through terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) staining. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected the messenger RNA (mRNA) levels. Western blot assay was conducted to measure the protein level. Enzyme-linked immunosorbent serologic assay examined tumor necrosis factor-α, interleukin (IL)-6, IL-1β, malondialdehyde, superoxide dismutase, plasma glutathione peroxidase, and catalase levels. Breviscapine improved sevoflurane-induced cognitive dysfunctioning in rats. Breviscapine could play a suppressive role in apoptosis in the brain tissues of sevoflurane-induced rats. Further functional analysis showed that sevoflurane increased inflammation and oxidative stress in the brain tissues of sevoflurane-induced rats whereas breviscapine exerted apposite effects on sevoflurane-induced inflammation and oxidative stress. Additionally, we demonstrated that breviscapine promoted sevoflurane-induced phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) (PI3K/Akt) pathway and inhibited sevoflurane-induced nuclear factor kappa B (NF-κB) pathway in the brain tissues of rats. These results indicate that breviscapine could improve sevoflurane-induced cognitive dysfunction through activating the PI3K/Akt pathway and suppressing NF-κB pathway, which provides a therapeutic method for patients with sevoflurane-induced cognitive dysfunction.
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