七氟醚通过AMPK-SIRT1-NF-κB通路调节细胞自噬对大鼠颅脑损伤的神经保护作用

doi:10.3969/j.issn.1006-6233.2025.03.05

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Abstract Objective: To investigate the neuroprotective effect of sevoflurane (Sevo) on rat with traumatic brain injury (TBI) by regulating cellular autophagy through the AMP-activated protein kinase (AMPK)/silent mating type information regulator 2 homolog 1 (SIRT1)-nuclear factor kappa B (NF-κB) pathway. Methods: The successfully modeled TBI rats were grouped into TBI group, L-Sevo, M-Sevo, H-Sevo (inhalation of 2L/min O₂ + 1%, 2%, 4% Sevo + intraperitoneal injection of 2mg/kg normal saline), and Sevo+Compound C (inhalation of 2L/min O₂ + 4% Sevo + intraperitoneal injection of 2mg/kg AMPK inhibitor Compound C). Additionally, 6 rats were selected as the Sham group. The Sham and TBI groups inhaled 2L/min O₂+ injected an equal amount of normal saline, both inhaling gas for 6 hours, with 6 rats in each group. The modified neurological severity score (mNSS) was applied to evaluate the degree of neurological deficits in TBI rats. Nissl staining was applied to observe the pathological condition of rat cortical tissue. Transmission electron microscopy was applied to observe autophagy in rat cortical tissue cells. TUNEL staining was applied to observe apoptosis of cortical tissue cells in rats. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the expression of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) in rat blood. Western blot was applied to detect the expression of p-AMPK, AMPK, SIRT1, NF-κB, LC3II, LC3I, and p62 proteins in the cortical tissue of TBI rats. Results: The mNSS score, autophagic vacuole count, apoptosis rate, TNF-α, IL-1β, NF-κB, and p62 in the TBI group were significantly higher than those of the Sham group, while the numbers of nissl bodies, p-AMPK/AMPK, SIRT1, and LC3II/I were significantly lower than those of the Sham group (P<0.05). The mNSS score, apoptosis rate, TNF-α, IL-1β, NF-κB, and p62 in the L-Sevo, M-Sevo, and H-Sevo groups were significantly lower than those of the Sham group, while the number of nissl bodies and autophagic vacuoles, p-AMPK/AMPK, SIRT1, and LC3II/I were significantly higher than those of the TBI group (P<0.05). The mNSS score, apoptosis rate, TNF-α, IL-1β, NF-κB, and p62 in the Sevo+Compound C group were significantly higher than those in the H-Sevo group, while the number of nissl bodies and autophagic vacuoles, p-AMPK/AMPK, SIRT1, and LC3II/I were significantly lower than those of the H-Sevo group (P<0.05). Conclusion: Sevoflurane may regulate cellular autophagy and exert neuroprotective effects in TBI rats by modulating the AMPK-SIRT1-NF-κB pathway.

Key words： Sevoflurane AMP-activated protein kinase Silent mating type information regulator 2 homolog 1 Nuclear factor kappa B Autophagy Brain injury Neuroprotection

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2025.03.05 OR http://www.hbyxzzs.cn/EN/Y2025/V31/I3/380

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