挥发性麻醉药物对巨噬细胞吞噬作用的影响
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Volatile anesthetics affect macrophage phagocytosis
背景与目的
围手术期感染，特别是手术部位感染引起显着的发病率和死亡率。吞噬作用是去除微生物的关键步骤。我们检测了常用麻醉药对巨噬细胞吞噬作用的影响及其机制。
方 法
采用RAW264.7小鼠细胞，小鼠腹腔巨噬细胞和THP-1人细胞检测麻醉药（异氟醚，七氟醚，异丙酚）对巨噬细胞吞噬功能的影响。将受调理的绵羊红细胞或荧光标记的大肠杆菌用作吞噬细胞。Rap1是吞噬作用中的关键蛋白，使用活性Rap1和检测试剂盒评估Rap1的活化。使用azi-异氟烷和azi-七氟醚进行光学标记实验监测Rap1上的麻醉剂结合位点。以Rap1的丙氨酸扫描以评估麻醉剂结合位点在Rap1活化和吞噬作用中的诱变作用。
结 果
异氟醚和七氟醚暴露后，巨噬细胞吞噬功能明显减弱，而异丙酚则没有（1％异氟醚减少50％,1.5％七氟醚减少50％）。光标记实验表明，七氟醚直接与Rap1结合。诱变分析表明，七氟醚结合位点影响Rap1活化和巨噬细胞吞噬作用。
结 论
我们发现异氟醚和七氟醚减弱了巨噬细胞的吞噬作用，但异丙酚却没有。
原始文献摘要
Zha Hui,Matsunami Erika,Blazon-Brown Nathan et al. Volatile anesthetics affect macrophage phagocytosis.[J] .PLoS ONE, 2019, 14: e0216163.
BACKGROUND Perioperative infections, particularly surgical site infections pose significant morbidity and mortality. Phagocytosis is a critical step for microbial eradication. We examined the effect of commonly used anesthetics on macrophage phagocytosis and its mechanism.
METHODS The effect of anesthetics (isoflurane, sevoflurane, propofol) on macrophage phagocytosis was tested using RAW264.7 mouse cells, mouse peritoneal macrophages, and THP-1 human cells. Either opsonized sheep erythrocytes or fluorescent labeled Escherichia coli were used as phagocytic objects. The activation of Rap1, a critical protein in phagocytosis was assessed using the active Rap1 pull-down and detection kit. To examine anesthetic binding site(s) on Rap1, photolabeling experiments were performed using azi-isoflurane and azi-sevoflurane. The alanine scanning mutagenesis of Rap1 was performed to assess the role of anesthetic binding site in Rap1 activation and phagocytosis.
RESULTS Macrophage phagocytosis was significantly attenuated by the exposure of isoflurane (50% reduction by 1% isoflurane) and sevoflurane (50% reduction by 1.5% sevoflurane), but not by propofol. Photolabeling experiments showed that sevoflurane directly bound to Rap1. Mutagenesis analysis demonstrated that the sevoflurane binding site affected Rap1 activation and macrophage phagocytosis.
CONCLUSIONS We showed that isoflurane and sevoflurane attenuated macrophage phagocytosis, but propofol did not. Our study showed for the first time that sevoflurane served as a novel small GTPase Rap1 inhibitor. The finding will further enrich our understanding of yet-to-be determined mechanism of volatile anesthetics and their off-target effects. The sevoflurane binding site was located outside the known Rap1 functional sites, indicating the discovery of a new functional site on Rap1 and this site would serve as a pocket for the development of novel Rap1 inhibitors.
麻醉学文献进展分享
贵州医科大学高鸿教授课题组
翻译：符校魁 编辑：何幼芹 审校：王贵龙