Li D S, Raybould H E, Quintero E, Guth P H
Department of Medicine, University of California, Los Angeles.
Gastroenterology. 1992 Apr;102(4 Pt 1):1124-8.
Disruption of the gastric mucosal barrier with resultant increased acid back-diffusion leads to a marked increase in gastric mucosal blood flow (GMBF). This increase in GMBF is blocked by ablation of capsaicin-sensitive sensory neurons. The gastric arterioles are densely innervated by afferent neurons containing vasodilator peptides, calcitonin gene-related peptide (CGRP) being the most potent of these. We investigated (a) whether CGRP is the vasodilator mediator released by acid stimulation of capsaicin-sensitive sensory neurons and (b) whether the resultant hyperemia protects against the acid-induced mucosal injury. When the stomach was perfused with 0.15N HCl plus 15% ethanol, GMBF significantly increased by 70%. This hyperemic response was completely blocked by intra-arterial infusion of human CGRP8-37 (500 pmol/min), a CGRP-receptor antagonist, close to the stomach. With the blockade of the hyperemic response to acid back-diffusion, gross and histological mucosal damage were significantly aggravated. It is concluded that CGRP mediates the gastric hyperemic response to acid back-diffusion and that this gastric hyperemic response is an important protective factor against acid-induced injury.
胃黏膜屏障破坏导致酸反向弥散增加，进而引起胃黏膜血流量（GMBF）显著增加。辣椒素敏感感觉神经元的消融可阻断GMBF的这种增加。胃小动脉由含有血管舒张肽的传入神经元密集支配，其中降钙素基因相关肽（CGRP）最为有效。我们研究了（a）CGRP是否为酸刺激辣椒素敏感感觉神经元释放的血管舒张介质，以及（b）由此产生的充血是否能预防酸诱导的黏膜损伤。当胃用0.15N HCl加15%乙醇灌注时，GMBF显著增加70%。这种充血反应被在胃附近动脉内输注人CGRP8 - 37（500 pmol/分钟）（一种CGRP受体拮抗剂）完全阻断。随着对酸反向弥散充血反应的阻断，肉眼和组织学上的黏膜损伤显著加重。结论是CGRP介导胃对酸反向弥散的充血反应，且这种胃充血反应是预防酸诱导损伤的重要保护因素。
