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）刺激胃酸分泌，研究了胃酸分泌状态下大鼠胃黏膜防御能力的波动。在刺激胃酸分泌的剂量下，Hi （3 ~ 20 mg/kg,s.c）可保护胃黏膜免受0.6 N盐酸引起的胃损伤，抑制胃运动，增加胃内碱性分泌，但不增加十二指肠碱性分泌。盐酸西咪替丁（一种H2拮抗剂）和吲哚美辛（一种环加氧酶抑制剂）显著减弱了Hi的这些作用，这表明H2受体和内源性前列腺素（pg）参与了Hi的作用。另一方面，在高剂量16,16-二甲基PGE2 （dmPGE2: 10-30 ug/kg）存在下，单剂量Hi （40-80 mg/kg）显著增强胃粘膜微血管通透性，导致出血性粘膜损伤，且连续4天重复使用这两种药物可产生严重的胃粘膜病变。hi （20 mg/kg）对胃黏膜原有病变也有有害影响，并显著延迟0.6 N盐酸诱导病变的愈合。综上所述，在酸刺激状态下，粘膜防御能力的增强除了与酸分泌过程直接相关外，还可能通过内源性pg通过H2受体介导的机制。Hi本身可能不是致溃疡物质，可能与内源性pg协同参与胃粘膜稳态的调节机制；他们一起工作，根据情况相互对抗。

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.