Tuinhout Rozemarijn S, Jongman Rianne M, Nieuwenhuijs-Moeke Gertrude J, Abdulahad Wayel H, Struys Michel M R F, van Meurs Matijs, Bosch Dirk J
Department of Anesthesiology, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, 9700 RB, Groningen, Netherlands.
Department of Pathology & Medical Biology, Laboratory for Endothelial Biomedicine & Vascular Drug Targeting Research, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Can J Anaesth. 2025 Aug;72(8):1291-1304. doi: 10.1007/s12630-025-03025-y. Epub 2025 Aug 4.
The vascular endothelium is known to modulate the inflammatory response during surgery. Sevoflurane has been shown to protect against tumor necrosis factor alpha (TNF-α)-induced endothelial dysfunction, but the effects of other anesthetics or combinations with opioids on endothelial response are unclear.
In this in vitro study, we stimulated human umbilical vein endothelial cells with TNF-α (10 ng·mL) in triplicate in three independent experiments and treated them with sevoflurane (0.8%, 2.0%, and 4.0%), propofol (2, 5, and 10 μg·mL), remifentanil (2, 5, and 10 ng·mL) and fentanyl (0.5, 1.5, and 5 ng·mL) individually and in combinations. We evaluated the expression levels of endothelial adhesion molecules and proinflammatory cytokines using reverse transcription quantitative real-time polymerase chain reaction, Western blotting, and the enzyme-linked immunosorbent assay.
Only sevoflurane significantly diminished the messenger ribonucleic acid (mRNA) and protein expression of adhesion molecules in the presence of TNF-α (E-selectin [sevoflurane 0.8%, P < 0.001; 2%, P = 0.03; 4%, P = 0.004], vascular cell adhesion molecule 1 [sevoflurane 0.8%, P < 0.001; 2%, P = 0.002; 4%, P < 0.001], and intercellular adhesion molecule 1 [sevoflurane 0.8%, P = 0.002; 2%, P = 0.007; 4%, P < 0.001]). Additionally, mRNA and protein expression of the proinflammatory cytokines interleukin [IL]-6 and IL-8 decreased after exposure to sevoflurane alone for (IL-6 mRNA: sevoflurane 0.8%, P = 0.004; 4%, P < 0.001; IL-8 mRNA: sevoflurane 4%, P = 0.02; IL-6 protein: sevoflurane 0.8%, P < 0.001; 2%, P = 0.003; 4%, P < 0.001; IL-8 protein: sevoflurane 0.8%, P = 0.03; 2%, P < 0.001; 4%, P = 0.008]). The addition of opioids did not change the expression in either of the adhesion molecules or inflammatory cytokines.
In this exploratory study, sevoflurane inhibited endothelial adhesion molecules and proinflammatory response in vitro, whereas propofol, remifentanil, or fentanyl did not possess the same effect. While the effects in vivo are unknown, these findings might highlight the potential impact of anesthetic choice on modulating the inflammatory response of endothelial cells.
已知血管内皮在手术过程中可调节炎症反应。七氟醚已被证明可预防肿瘤坏死因子α（TNF-α）诱导的内皮功能障碍，但其他麻醉剂或与阿片类药物联合使用对内皮反应的影响尚不清楚。
在这项体外研究中，我们在三个独立实验中用TNF-α（10 ng·mL）刺激人脐静脉内皮细胞三次重复，并分别用七氟醚（0.8%、2.0%和4.0%）、丙泊酚（2、5和10 μg·mL）、瑞芬太尼（2、5和10 ng·mL）和芬太尼（0.5、1.5和5 ng·mL）单独及联合处理。我们使用逆转录定量实时聚合酶链反应、蛋白质印迹法和酶联免疫吸附测定法评估内皮黏附分子和促炎细胞因子的表达水平。
仅七氟醚在TNF-α存在时显著降低了黏附分子的信使核糖核酸（mRNA）和蛋白质表达（E-选择素[七氟醚0.8%，P < 0.001；2%，P = 0.03；4%，P = 0.004]，血管细胞黏附分子1[七氟醚0.8%，P < 0.001；2%，P = 0.002；4%，P < 0.001]，细胞间黏附分子1[七氟醚0.8%，P = 0.002；2%，P = 0.007；4%，P < 0.001]）。此外，单独暴露于七氟醚后促炎细胞因子白细胞介素[IL]-6和IL-8的mRNA和蛋白质表达降低（IL-6 mRNA：七氟醚0.8%，P = 0.004；4%，P < 0.001；IL-8 mRNA：七氟醚4%，P = 0.02；IL-6蛋白质：七氟醚0.8%，P < 0.001；2%，P = 0.003；4%，P < 0.001；IL-8蛋白质：七氟醚0.8%，P = 0.03；2%，P < 0.001；4%，P = 0.008]）。添加阿片类药物未改变黏附分子或炎症细胞因子中的任何一种的表达。
在这项探索性研究中，七氟醚在体外抑制了内皮黏附分子和促炎反应，而丙泊酚、瑞芬太尼或芬太尼没有相同的作用。虽然体内作用尚不清楚，但这些发现可能突出了麻醉选择对调节内皮细胞炎症反应的潜在影响。
