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目的 基于转录因子MAF碱性亮氨酸拉链转录因子B/双特异性磷酸酶14(MAFB/DUSP14)轴探讨七氟醚在动脉瘤栓塞麻醉中的脑保护作用。方法 将SD大鼠随机分为对照组、模型组、七氟醚组、七氟醚+AAV-NC组和七氟醚+shMAFB组。采用线栓法建立大脑中动脉阻塞（MCAO）模型，七氟醚组于再灌注时吸入2.4%七氟醚2 h。通过Longa评分评估神经功能，TTC染色法测定脑梗死体积，Western blot法检测MAFB、DUSP14、p-JNK、JNK、p-p38及p38蛋白表达，ELISA法测定肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)及IL-6含量，生化法检测超氧化物歧化酶（SOD）活性与丙二醛（MDA）水平，TUNEL/NeuN共染色法分析神经元凋亡情况。结果 与对照组比较，模型组大鼠神经功能缺损评分与脑梗死体积均显著增加（P<0.05），脑组织中MAFB、DUSP14蛋白表达显著下降（P<0.05）,p-JNK/JNK与p-p38/p38比值显著升高（P<0.05），促炎因子TNF-α、IL-1β、IL-6及MDA含量显著上升（P<0.05）,SOD活性显著降低（P<0.05），神经元凋亡比例显著升高（P<0.05）。与模型组比较，七氟醚组上述指标均获显著改善（P<0.05）。而七氟醚+shMAFB组各指标较七氟醚组出现显著逆转（P<0.05）。结论 七氟醚可能通过上调MAFB，促进DUSP14表达，进而抑制JNK/p38 MAPK信号通路，减轻神经炎症、氧化应激及神经元凋亡，最终发挥脑保护作用。
Abstract：AIM To explore the cerebral protective effect of sevoflurane during aneurysm for embolization anesthesia via the MAF bZIP transcription factor B/dual specificity phosphatase 14(MAFB/DUSP14) axis. METHODS SD rats were randomly divided into the control group, model group, sevoflurane group, sevoflurane + shMAFB group, and sevoflurane + AAV-NC group. A middle cerebral artery occlusion model was established using the suture method. The sevoflurane group received 2.4% sevoflurane inhalation for 2 h during reperfusion. Neurological function was assessed using the Longa score, cerebral infarction volume was measured by TTC staining, protein expressions of MAFB, DUSP14, p-JNK, JNK, p-p38, and p38 were detected by Western blot, levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and IL-6 were measured by ELISA, superoxide dismutase(SOD) activity and malondialdehyde(MDA) levels were determined by biochemical methods, and neuronal apoptosis was analyzed by TUNEL/NeuN co-staining. RESULTS Compared with the control group, the model group showed significant increases in neurological deficit scores and cerebral infarction volume(P < 0.05), significant decreases in MAFB and DUSP14 protein expression in brain tissue(P < 0.05), significant increases in the ratios of p-JNK/JNK and p-p38/p38(P < 0.05), significant elevations in pro-inflammatory factors TNF-α, IL-1β, IL-6, and MDA levels(P < 0.05), significant reduction in SOD activity(P < 0.05), and a significant increase in neuronal apoptosis rate(P < 0.05). Compared with the model group, the sevoflurane group showed significant improvements in all the above indicators(P < 0.05). However, all indicators in the sevoflurane + shMAFB group were significantly reversed compared to the sevoflurane group(P < 0.05). CONCLUSION Sevoflurane postconditioning may exert cerebral protective effects by upregulating MAFB and promoting DUSP14 expression, thereby inhibiting the JNK/p38 MAPK signaling pathway, and alleviating neuroinflammation, oxidative stress, and neuronal apoptosis.
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基本信息:
DOI：10.19577/j.1007-4406.2026.08.004
中图分类号:R614
引用信息:
[1]希尔娜衣·艾孜买提,尤吐孜阿衣,戴庆,等.基于MAFB/DUSP14轴探讨七氟醚在动脉瘤栓塞麻醉中的脑保护作用[J].中国临床药学杂志,2026,35(08):692-698.DOI:10.19577/j.1007-4406.2026.08.004.
基金信息:
新疆维吾尔自治区自然科学基金资助项目（编号2022D01C753）
2026-08-25
2026-08-25