Tepperman B L, Vozzolo B L, Soper B D
Department of Physiology, Faculty of Medicine, University of Western Ontario, London, Canada.
Dig Dis Sci. 1993 Nov;38(11):2056-61. doi: 10.1007/BF01297085.
The present study examined the interaction between neutrophils and gastric mucosal nitric oxide (NO) synthesis in the regulation of gastric mucosal integrity in the rat. Male Sprague-Dawley rats were made neutropenic by intraperitoneal injections of methotrexate (MT; 2.5 mg/kg) or antineutrophil serum (ANS; 100 microliters). Control rats were treated with saline. Neutropenia was confirmed by circulating neutrophil counts and tissue myeloperoxidase activity. Neutropenic or control rats were given 2 ml of ethanol (EtOH; 40% w/v intragastrically). Neutropenic rats were less susceptible to EtOH-induced mucosal damage when compared to control rats. Mucosal NO synthesis was increased in neutropenic rats. EtOH instillation reduced NO synthase in control rats. However, in MT-treated rats the reduced NO synthase activity was not different from that observed in untreated control rats.
(1) EtOH-mediated gastric mucosal injury appears to be a neutrophil-mediated process. (2) Neutropenia results in an increase in mucosal NO synthesis. (3) MT treatment augments the degree of mucosal integrity. The increase in integrity is associated with a reduction in mucosal neutrophil infiltration as well as maintenance of NO synthase activity. ANS appears to influence mucosal integrity primarily by a reduction in circulating neutrophils.
本研究检测了大鼠胃黏膜完整性调节过程中中性粒细胞与胃黏膜一氧化氮（NO）合成之间的相互作用。通过腹腔注射甲氨蝶呤（MT；2.5mg/kg）或抗中性粒细胞血清（ANS；100微升）使雄性Sprague-Dawley大鼠中性粒细胞减少。对照大鼠用生理盐水处理。通过循环中性粒细胞计数和组织髓过氧化物酶活性确认中性粒细胞减少。给中性粒细胞减少或对照大鼠胃内注射2ml乙醇（EtOH；40%w/v）。与对照大鼠相比，中性粒细胞减少的大鼠对EtOH诱导的黏膜损伤更不敏感。中性粒细胞减少的大鼠黏膜NO合成增加。EtOH灌注降低了对照大鼠的NO合酶。然而，在MT处理的大鼠中，降低的NO合酶活性与未处理的对照大鼠中观察到的没有差异。
（1）EtOH介导的胃黏膜损伤似乎是一个中性粒细胞介导的过程。（2）中性粒细胞减少导致黏膜NO合成增加。（3）MT处理增强了黏膜完整性的程度。完整性的增加与黏膜中性粒细胞浸润的减少以及NO合酶活性的维持有关。ANS似乎主要通过循环中性粒细胞的减少来影响黏膜完整性。
