Pharmacological Studies on Gastric Mucosal Defense Mechanisms;Why doesn't the stomach digest itself?

点击翻译按钮获取中文摘要

This grant supported to find the following evidence;1)Establishment of quantitative assay system of gastric mucosal bleeding:The numbers of the erythrocytes leaked into the perfusate was measured in the consciuos rat provided with gastric cannula in order to evaluate the degree of gastric hemorrhage. Restraint stress itself caused gastric mucosal damage and the concomitant administration of indomethacin or aspirin significantly exacerbated gastric mucosal bleeding. We concluded this model could be useful for the study of gastric mucosal defense mechanisms.2)Drug effects;Antisecretory drugs, histamine H_2-receptor antagonists,an anticholinergic,and proton pump inhibitors,effectively prevented the gastric mucosal bleeding caused by indomethacin. And several types of antiulcer drugs which have weak antisecretory activities and increase the mucosal defense mechanisms also protected the stomach from the mucosal lesions. Central depressants were also effective to prevent gastric bleeding. Th … More ese imply that not only gastric aggressive and defense mechanisms but also neural factors may have significant roles for gastric mucosal integrity.3)Adverse(unexpected) effects of the drugs:Antitumor drugs,antibiotics,oral hypoglycemic drugs and drugs acting on cardiovascular systems also resulted in gastric mucosal bleeding, suggesting that gastric mucosa is susceptive to exogenous chemicals.4)Changes in tissue protease activity with respect to ulcer formation; pepsinogen is one of the representative acidic protease and has been studied. However,there is few report on the role of intracellular proteases in relation to the pathogenesis of gastrointestinal ulcers. The neutral protease activity in the gastric tissue was determined with special reference to the development of gastric ulcers. Water-immersion restraint (stress) caused gastric mucosal lesions or ulcers 2 hours after the stress exposure. The tissue enzyme activity was already stimulated 15 and 30 min after the stress, suggesting that the stress may act intracellulanly to activate the neutral proteases and this may be involved in digestion of cellular membranes to cause mucosal damages. This hypothesis should be studied more precisely in terms of protease inhibitors.The followings are still open to be studied;1)Tissue levels of high-energy-related phosphor compounds with respect to the development and curative stage of gastric ulcers2)Relation between mucosal resistance and gastric function3)What's the major factor in mucosal defense mechanisms and how is the control or regulation mechanism of "the defense"? Less