Oliveira Tainá B, Braga Cassia L, Battaglini Denise, Pelosi Paolo, Rocco Patricia R M, Silva Pedro L, Cruz Fernanda F
Laboratory of Pulmonary Investigation, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Anesthesia and Critical Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, University of Genoa, Genoa, Italy.
Front Med (Lausanne). 2023 Jul 27;10:1225179. doi: 10.3389/fmed.2023.1225179. eCollection 2023.
Patients with sepsis often require sedation and/or anesthesia. Although the immunomodulatory effects of anesthetics have been increasingly recognized, the molecular mechanisms require better elucidation. We compared the effects of sevoflurane with propofol on the expression of pro- and anti-inflammatory biomarkers released by monocytes/macrophages and blood/bronchoalveolar lavage fluid (BALF) neutrophils, the phagocytic capacity of monocytes/ macrophages, and neutrophil migration, as well as mediators associated with alveolar epithelial and endothelial cells obtained from rats with sepsis.
Polymicrobial sepsis was induced by cecal ligation and puncture in nine male Wistar rats. After 48 h, animals were euthanized and their monocytes/alveolar macrophages, blood and BALF neutrophils, as well as alveolar epithelial and endothelial cells were extracted, and then exposed to (1) sevoflurane (1 minimal alveolar concentration), (2) propofol (50 μM), or (3) saline, control (CTRL) for 1 h.
Sevoflurane reduced interleukin (IL)-6 mRNA expression in monocytes and alveolar macrophages ( = 0.007, = 0.029), whereas propofol decreased IL-6 mRNA only in alveolar macrophages ( = 0.027) compared with CTRL. Sevoflurane increased IL-10 expression ( = 0.0002) in monocytes compared with propofol and increased IL-10 mRNA and transforming growth factor (TGF)-β mRNA ( = 0.037, = 0.045) compared with CTRL. Both sevoflurane and propofol did not affect mRNA expression of IL-10 and TGF-β in alveolar macrophages. The phagocytic capacity of monocytes ( = 0.0006) and alveolar macrophages ( = 0.0004) was higher with sevoflurane compared with propofol. Sevoflurane, compared with CTRL, reduced IL-1β mRNA ( = 0.003, = 0.009) and C-X-C chemokine receptor 2 mRNA (CXCR2, = 0.032 and = 0.042) in blood and BALF neutrophils, and increased CXCR4 mRNA only in BALF neutrophils ( = 0.004). Sevoflurane increased blood neutrophil migration ( = 0.015) compared with propofol. Both sevoflurane and propofol increased zonula occludens-1 mRNA ( = 0.046, = 0.003) in alveolar epithelial cells and reduced Toll-like receptor 4 mRNA ( = 0.043, = 0.006) in alveolar endothelial cells compared with CTRL. Only propofol reduced surfactant protein B mRNA ( = 0.028) in alveolar epithelial cells.
Sevoflurane, compared with propofol, increased anti-inflammatory biomarkers in monocytes, but not in alveolar macrophages, enhanced monocyte/alveolar macrophage phagocytic capacity and increased neutrophil migration in experimental sepsis. Both propofol and sevoflurane protected lung epithelial and endothelial cells.
脓毒症患者常需要镇静和/或麻醉。尽管麻醉剂的免疫调节作用已得到越来越多的认识，但其分子机制仍需进一步阐明。我们比较了七氟醚和丙泊酚对单核细胞/巨噬细胞及血液/支气管肺泡灌洗液（BALF）中性粒细胞释放的促炎和抗炎生物标志物表达、单核细胞/巨噬细胞的吞噬能力、中性粒细胞迁移以及脓毒症大鼠肺泡上皮细胞和内皮细胞相关介质的影响。
通过对9只雄性Wistar大鼠进行盲肠结扎和穿刺诱导多微生物脓毒症。48小时后，对动物实施安乐死并提取其单核细胞/肺泡巨噬细胞、血液和BALF中性粒细胞以及肺泡上皮细胞和内皮细胞，然后将其暴露于（1）七氟醚（1个最低肺泡浓度）、（2）丙泊酚（50μM）或（3）生理盐水对照组（CTRL）中1小时。
与CTRL相比，七氟醚降低了单核细胞和肺泡巨噬细胞中白细胞介素（IL）-6 mRNA的表达（=0.007，=0.029），而丙泊酚仅降低了肺泡巨噬细胞中IL-6 mRNA的表达（=0.027）。与丙泊酚相比，七氟醚增加了单核细胞中IL-10的表达（= =0.0002），与CTRL相比增加了IL-10 mRNA和转化生长因子（TGF）-β mRNA（=0.037，=0.045）。七氟醚和丙泊酚均未影响肺泡巨噬细胞中IL-10和TGF-β的mRNA表达。与丙泊酚相比，七氟醚处理的单核细胞（=0.0006）和肺泡巨噬细胞（=0.0004）的吞噬能力更高。与CTRL相比，七氟醚降低了血液和BALF中性粒细胞中IL-1β mRNA（=0.003，=0.009）和C-X-C趋化因子受体2 mRNA（CXCR2，=0.032和=0.042）的表达，仅增加了BALF中性粒细胞中CXCR4 mRNA的表达（=0.004）。与丙泊酚相比，七氟醚增加了血液中性粒细胞迁移（=0.015）。与CTRL相比，七氟醚和丙泊酚均增加了肺泡上皮细胞中闭合蛋白-1 mRNA的表达（=0.046，=0.003），并降低了肺泡内皮细胞中Toll样受体4 mRNA的表达（=0.043，=0.006）。只有丙泊酚降低了肺泡上皮细胞中表面活性蛋白B mRNA的表达（=0.028）。
与丙泊酚相比，七氟醚增加了单核细胞而非肺泡巨噬细胞中的抗炎生物标志物，增强了单核细胞/肺泡巨噬细胞的吞噬能力，并增加了实验性脓毒症中的中性粒细胞迁移。丙泊酚和七氟醚均对肺上皮细胞和内皮细胞有保护作用。
