Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Pulm Pharmacol Ther. 2024 Sep;86:102312. doi: 10.1016/j.pupt.2024.102312. Epub 2024 Jun 19.
Acute lung injury (ALI) frequently occurs after video-assisted thoracoscopic surgery (VATS). Ferroptosis is implicated in several lung diseases. Therefore, the disparate effects and underlying mechanisms of the two commonly used anesthetics (sevoflurane (Sev) and propofol) on VATS-induced ALI need to be clarified. In the present study, enrolled patients were randomly allocated to receive Sev (group S) or propofol anesthesia (group P). Intraoperative oxygenation, morphology of the lung tissue, expression of ZO-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), glutathione (GSH), Fe, glutathione peroxidase 4 (GPX4), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in the lung tissue as well as the expression of TNF-α and IL-6 in plasma were measured. Postoperative complications were recorded. Of the 85 initially screened patients scheduled for VATS, 62 were enrolled in either group S (n = 32) or P (n = 30). Compared with propofol, Sev substantially (1) improved intraoperative oxygenation; (2) relieved histopathological lung injury; (3) increased ZO-1 protein expression; (4) decreased the levels of TNF-α and IL-6 in both the lung tissue and plasma; (5) increased the contents of GSH and SOD but decreased Fe concentration; (6) upregulated the protein expression of p-AKT, Nrf2, HO-1, and GPX4. No significant differences in the occurrence of postoperative outcomes were observed between both groups. In summary, Sev treatment, in comparison to propofol anesthesia, may suppress local lung and systemic inflammatory responses by activating the PI3K/Akt/Nrf2/HO-1 pathway and inhibiting ferroptosis. This cascade of effects contributes to the maintenance of pulmonary epithelial barrier permeability, alleviation of pulmonary injury, and enhancement of intraoperative oxygenation in patients undergoing VATS.
急性肺损伤（ALI）常发生在电视辅助胸腔镜手术后（VATS）。铁死亡与多种肺部疾病有关。因此，需要阐明两种常用麻醉剂（七氟醚（Sev）和异丙酚）对 VATS 诱导的 ALI 的不同作用及其潜在机制。在本研究中，纳入的患者被随机分配接受 Sev（S 组）或异丙酚麻醉（P 组）。术中氧合、肺组织形态、ZO-1、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、铁、谷胱甘肽过氧化物酶 4（GPX4）和磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）/核因子红细胞 2 相关因子 2（Nrf2）/血红素加氧酶-1（HO-1）在肺组织中的表达以及血浆中 TNF-α和 IL-6 的表达均进行了测量。记录术后并发症。在最初筛选的 85 例计划接受 VATS 的患者中，62 例被纳入 S 组（n=32）或 P 组（n=30）。与异丙酚相比，Sev 显著（1）改善术中氧合；（2）缓解组织病理学肺损伤；（3）增加 ZO-1 蛋白表达；（4）降低肺组织和血浆中 TNF-α和 IL-6 的水平；（5）增加 GSH 和 SOD 的含量，但降低 Fe 浓度；（6）上调 p-AKT、Nrf2、HO-1 和 GPX4 的蛋白表达。两组术后结局的发生率无显著差异。综上所述，与异丙酚麻醉相比，Sev 治疗可能通过激活 PI3K/Akt/Nrf2/HO-1 通路和抑制铁死亡来抑制局部肺和全身炎症反应。这一系列效应有助于维持肺上皮屏障通透性，减轻肺损伤，并增强接受 VATS 患者的术中氧合。
