Butorphanol attenuates inflammation via targeting NF-κB in septic rats with brain injury

J. Meng, S.-J. Jiang, D. Jiang, Y. Zhao

Department Anesthesiology, Affiliated Jining No. 1 People’s Hospital of Jining Medical University, Jining Medical University, Jining, China. 39588362@qq.com

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• Geriatrics

OBJECTIVE: To observe the therapeutic effect of butorphanol on brain tissue injury in rats with sepsis through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway.

MATERIALS AND METHODS: Sprague-Dawley rats were divided into control group (n=20), sepsis model group [cecal ligation and perforation (CLP) group, n=20], and butorphanol treatment group (n=20). After successful modeling, the blood and brain tissues were collected from rats at 24 h. The content of serum brain injury indexes was detected. Hematoxylin-eosin (HE) staining assay and enzyme-linked immunosorbent assay (ELISA) were separately carried out to observe the pathological changes and measure the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) activity. The neurological function was scored in rats. Glial fibrillary acidic protein (GFAP), S100, and NF-κB signaling pathway genes and proteins in brain tissues were detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blotting.

RESULTS: CLP group showed remarkably increased levels of serum glucosuria (GLU), creatinine (CR), and Na+ but an evidently reduced level of K+ in comparison with the control group (p<0.05), while the treatment group displayed contrary trends. Histopathological observations showed that the rats in the CLP group suffered a brain injury, while those in the treatment group had mild pathological changes. The MPO in the CLP group was significantly increased compared with that in the control group (p<0.05). The levels of TNF-α and IL-6 were overtly higher in the CLP group than those in the control group, and these indexes in the treatment group were close to those in the control group. The messenger ribonucleic acid (mRNA) expression levels of S100, GFAP, Toll-like receptor 2 (TLR2), and NF-κB in CLP group were evidently higher than those in the control group and treatment group (p<0.05). The results of Western blotting revealed that the protein expression of NF-κB was significantly higher in CLP group than that in the control group, and it declined in the treatment group, which was close to that in the control group.

CONCLUSIONS: Butorphanol can reduce the content of inflammatory factors TNF-α, IL-1, and IL-6 through the NF-κB signaling pathway, thereby relieving the brain injury caused by sepsis.

Published on: 2019/08/07

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