Fluctuations of the gastric mucosal defensive ability during acid secretory states: Protective and deleterious actions of histamine on the rat gastric mucosa

用组胺(Hi)作为胃酸分泌的刺激剂，研究了酸性服务状态下大鼠胃黏膜防御能力的变化。HI(3-20 mg/kg，S.C.)在刺激胃酸分泌的剂量下，可保护胃粘膜免受0.6N盐酸引起的胃损伤，抑制胃运动，增加胃的碱性分泌，但不增加十二指肠的碱性分泌。H2受体拮抗剂西咪替丁和环氧合酶抑制剂吲哚美辛均可显著减弱Hi的上述作用，提示H2受体和内源性前列腺素(PG)参与了Hi的上述作用。大剂量16，16-二甲基前列腺素E_2(dmPGE_2：10~30ug/kg)单次给药(40~80 mg/kg)可显著增加胃粘膜微血管通透性，引起出血性粘膜损伤，两药重复给药4d可引起严重的胃粘膜损伤。HI(20 mg/kg)对胃粘膜原有损伤也有不良影响，显著延缓0.6N盐酸损伤的愈合。综上所述，这些数据表明，在酸刺激状态下，除了与酸分泌过程直接相关的机制外，内源性PGs通过H2受体介导的机制可能会增强粘膜的防御能力。HI本身可能不是一种致溃疡物质，可能与内源性前列腺素一起参与胃粘膜内稳态的调节机制；它们共同工作，并根据情况相互拮抗。

Fluctuations of the gastric mucosal defensive ability during acid sercetory states were investigated in rats using histamine (Hi) as a stimulator of acid secretion. Hi (3-20 mg/kg,s.c.) at the doses which caused stimulation of acid secretion protected the gastric mucosa against 0.6 N HCl-induced gastric lesions, inhibited gastric motility, and increased alkaline secretion in the stomach but not in the duodenum. These actions of Hi were significantly attenuated by both cimetidine, an H2 antagonist, and indomethacin, a cyclooxygenase inhibitor, suggesting involvement of H2-receptors and endogenous prostaglandins (PGs). On the other hand, a single dose treatment of Hi (40-80 mg/kg) markedly enhanced the mucosal microvascular permeability of the stomach in the presence of high doses of 16,16-dimethyl PGE2 (dmPGE2: 10-30 ug/kg), resulting in hemorrhagic mucosal injury, and the repeated teatment with these two agents for 4 days produced severe lesions in the gastric mucosa. hi (20 mg/kg) also had a deleterious influence on the pre-existing lesions in the gastric mucosa and significantly delayed the healing of 0.6 N HCl-induced lesions. These data, all together, suggest that the mucosal defensive ability may be increased during acid stimulatory states, by the mechanisms mediated with endogenous PGs through H2 receptors in addition to those directly associated with the process of acid secretion. Hi by itself may not be an ulcerogenic substance and may be involved in the regulatory mechanism of the mucosal homeostasis in the stomach, in collaboration with endogenous PGs; they work together and antagonize each other, depending upon the situations.