A technique for the close-arterial administration of substances to the rat stomach in vivo has been developed. 2. Intra-arterial infusion of platelet-activating factor (Paf, 10-50 ng kg-1 min-1 for 10 min) induced macroscopically assessed damage in the corpus mucosa, characterized as vasocongestion and necrosis. 3. The threshold intra-arterial doses of Paf that induced histologically assessed damage in the antrum and corpus of the stomach (10 and 5 ng kg-1 min-1, respectively) produced minimal systemic hypotension (less than 20 mmHg) suggesting a dissociation between these events. 4. Pretreatment with the Paf-antagonist, L-652,731 (2.5 mg kg-1 i.v.) prevented the gastric damage induced by local infusion of Paf. 5. Intravenous infusion of Paf (25 ng kg-1 min-1) did not significantly damage the gastric mucosa, in contrast to the same dose infused locally, yet Paf administered by either route produced a comparable degree of hypotension. Such findings suggest minimal metabolism of Paf during its passage through the gastric circulation. 6. Local intra-arterial infusion of Paf in doses as low as 0.25 ng kg-1 min-1, which had no systemic hypotensive actions, significantly induced gastric damage in the presence of intragastric 20% ethanol. 7. These observations support a local role for Paf in the pathogenesis of gastric irritation and ulceration, such as that observed during endotoxin shock or bacterial infection. The present technique is thus useful for the study of locally administered substances on gastric function and integrity.
摘要
已开发出一种在大鼠体内向胃进行动脉内近距离给药的技术。2. 动脉内输注血小板活化因子（Paf，10 - 50 ng kg-1 min-1，持续10分钟）可引起胃体黏膜肉眼可见的损伤，表现为血管充血和坏死。3. 在胃窦和胃体引起组织学评估损伤的Paf动脉内阈值剂量（分别为10和5 ng kg-1 min-1）产生的全身低血压极小（小于20 mmHg），表明这些事件之间存在分离。4. 用Paf拮抗剂L-652,731（2.5 mg kg-1静脉注射）预处理可预防局部输注Paf引起的胃损伤。5. 静脉输注Paf（25 ng kg-1 min-1）与局部输注相同剂量相比，对胃黏膜无明显损伤，但两种途径给药的Paf产生的低血压程度相当。这些发现表明Paf在通过胃循环时代谢极少。6. 局部动脉内输注低至0.25 ng kg-1 min-1的Paf，在胃内存在20%乙醇的情况下，虽无全身降压作用，但可显著诱导胃损伤。7. 这些观察结果支持Paf在胃刺激和溃疡发病机制中起局部作用，如在内毒素休克或细菌感染期间观察到的那样。因此，本技术可用于研究局部给药物质对胃功能和完整性的影响。
