Fukatsu K, Saito H, Han I, Furukawa S, Lin M T, Matsuda T, Ikeda S, Inoue T, Yasuhara H, Muto T
Department of Surgery, University of Tokyo, Japan.
J Surg Res. 1998 Feb 1;74(2):119-24. doi: 10.1006/jsre.1997.5234.
As nitric oxide (NO) is an antiadhesive molecule, exogenous NO may modulate neutrophil adhesion in organs. This study was designed to examine the effects of the NO donor SNAP (S-nitroso-acetyl penicillamine) on neutrophil adhesion at the inflammatory site and in remote organs, in peritonitis using a fluorescent microscopic method.
In experiment 1, rats (n = 12) were given saline or 10 micrograms/kg of SNAP intravenously followed by continuous infusion of saline, or of 2, 20, or 200 micrograms/kg/h SNAP until sacrifice. Ten minutes after injection of saline or SNAP, 10(7) Escherichia coli were injected into the peritoneal cavity. Five hours after challenge, 10(6) fluorescein-labeled neutrophils were infused. Peritoneal samples, lungs, liver, and kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. In experiment 2, rats (n = 25) were treated with saline or 10 micrograms/kg of SNAP intravenously and infused with saline or 20 micrograms/kg/h SNAP; E. coli was injected as in experiment 1. Before or 5 h after challenge, hemodynamic data were obtained. Then, labeled neutrophils were infused for counting of neutrophil numbers in organs. Arterial blood gas data and the circulating neutrophil number were also determined.
Experiment 1. Twenty and 200 micrograms/kg/h SNAP infusions tended to reduce labeled neutrophil numbers in lungs, while all three SNAP doses decreased the peritoneal labeled neutrophil numbers.
Experiment 2. Five hours after bacterial injection, SNAP infusion simultaneously decreased both pulmonary and peritoneal labeled neutrophil numbers. SNAP had no effect on hemodynamic and blood gas data, or on circulating neutrophil numbers.
NO donors may be useful for preventing neutrophil-associated lung injury, but should be used with caution in light of the possible adverse effects on host defense in the peritoneal cavity.
由于一氧化氮(NO)是一种抗黏附分子,外源性NO可能调节器官中的中性粒细胞黏附。本研究旨在使用荧光显微镜法,研究NO供体S-亚硝基乙酰青霉胺(SNAP)对腹膜炎炎症部位及远处器官中性粒细胞黏附的影响。
在实验1中,给12只大鼠静脉注射生理盐水或10微克/千克的SNAP,随后持续输注生理盐水,或2、20或200微克/千克/小时的SNAP直至处死。注射生理盐水或SNAP 10分钟后,向腹腔内注射10⁷大肠杆菌。攻击后5小时,输注10⁶荧光素标记的中性粒细胞。采集腹膜样本、肺、肝和肾,在落射荧光显微镜下计数标记的中性粒细胞。在实验2中,给25只大鼠静脉注射生理盐水或10微克/千克的SNAP,并输注生理盐水或20微克/千克/小时的SNAP;如实验1中那样注射大肠杆菌。在攻击前或攻击后5小时,获取血流动力学数据。然后,输注标记的中性粒细胞以计数器官中的中性粒细胞数量。还测定动脉血气数据和循环中性粒细胞数量。
实验1。输注20和200微克/千克/小时的SNAP倾向于减少肺中标记的中性粒细胞数量,而所有三个SNAP剂量均降低了腹膜中标记的中性粒细胞数量。
实验2。细菌注射后5小时,输注SNAP同时降低了肺和腹膜中标记的中性粒细胞数量。SNAP对血流动力学和血气数据或循环中性粒细胞数量没有影响。
NO供体可能有助于预防中性粒细胞相关的肺损伤,但鉴于其可能对腹腔内宿主防御产生的不良影响,应谨慎使用。