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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摘要 目的: 探讨七氟醚(Sevo)通过单磷酸腺苷活化蛋白激酶(AMPK)/沉默信息调节因子2同系物1(SIRT1)-核因子κB(NF-κB)通路调节细胞自噬对大鼠颅脑损伤(TBI)的神经保护作用。方法: 将建模成功的TBI大鼠分为TBI组、L-Sevo、M-Sevo、H-Sevo(吸入2L/min O₂+1%、2%、4%的Sevo腹腔注射2mg/kg生理盐水)、Sevo+Compound C(吸入2L/min O₂+4%的Sevo+腹腔注射2mg/kg AMPK抑制剂Compound C),另选择6只大鼠为Sham组,Sham和TBI组吸入2L/min O₂+注射等量的生理盐水,均吸入气体6h,每组6只。mNSS评分评估TBI大鼠的神经功能缺损程度;尼氏染色观察大鼠大脑皮质组织病理情况;透射电镜观察大鼠大脑皮质组织细胞自噬;TUNEL染色观察大鼠大脑皮质组织细胞凋亡;ELISA检测大鼠血液中TNF-α、IL-1β的表达;Western blot检测TBI大鼠大脑皮质组织中p-AMPK、AMPK、SIRT1、NF-κB、LC3Ⅱ、LC3Ⅰ、p62蛋白的表达。结果: TBI组mNSS评分、自噬空泡数、凋亡率、TNF-α、IL-1β、NF-κB、p62高于Sham组,尼氏体数量、p-AMPK/AMPK、SIRT1、LC3Ⅱ/Ⅰ低于Sham组(P<0.05);L-Sevo、M-Sevo、H-Sevo组,mNSS评分、凋亡率、TNF-α、IL-1β、NF-κB、p62低于Sham组,尼氏体数量、自噬空泡数、p-AMPK/AMPK、SIRT1、LC3Ⅱ/Ⅰ高于TBI组(P<0.05);Sevo+Compound C组mNSS评分、凋亡率、TNF-α、IL-1β、NF-κB、p62高于H-Sevo组,尼氏体数量、自噬空泡数、p-AMPK/AMPK、SIRT1、LC3Ⅱ/Ⅰ低于H-Sevo组(P<0.05)。结论: 七氟醚可能通过调控AMPK-SIRT1-NF-κB通路调节细胞自噬,对TBI大鼠发挥神经保护作用。

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关键词 ：七氟醚, 单磷酸腺苷活化蛋白激酶, 沉默信息调节因子2同系物1, 核因子κB, 自噬, 颅脑损伤, 神经保护

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

基金资助:河北省 2022年度医学科学研究课题,(编号:20220360)

通讯作者: 杨强

引用本文:

李春雷, 李妍, 崔文斌, 杨强, 金治宾, 梁赞. 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[J]. 河北医学, 2025, 31(3): 380-385.
LI Chunlei, LI Yan, CUI Wenbin, et al. Sevoflurane Regulates Cellular Autophagy and Exerts Neuroprotective Effects in Traumatic Brain Injury Rats via the Modulation of the AMPK-SIRT1-NF-κB Pathway. HeBei Med, 2025, 31(3): 380-385.

链接本文:

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

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