Pharmacological Study on Analysis of Gastric Mucosal Defensive Mechanisms and Cytoprotective Action of Drugs

对胃粘膜防御机制及其相关药物作用进行了研究。研究结果如下：1.胃粘膜防御功能的药物评价。失血性休克或应用血小板活化因子(PAF)造成胃粘膜损伤。药物试验(前列腺素、自主药物、蔚蓝化合物)表明，自主因素和超氧化物的产生与前者的特征有关，而血管因素与后者的特征密切相关。炎症反应可能与PAF引起的胃损伤有关。此外，还建立了通过测量胃电势差(PD)来评价与防御机制有关的药物的方法。胃PD对损伤胃粘膜的因素或物质非常敏感。用这种方法，可以明显地证明甘草酮和氨水诱导的粘膜刺激的有效性。2.药物评价…更多的是关于胃血流的。建立了分离灌流全胃制剂的方法。使用这种方法，内皮素被发现能有效并持续地产生血管收缩。另一方面，一种天青烯类化合物能增加麻醉大鼠的胃血流量。3.关于细胞保护作用的药物评价。在分离的悬浮胃粘膜细胞和麻醉大鼠的胃粘膜上，测定了乙醇损伤对细胞内酶的释放。在这两种方法中，甘草酮都具有细胞保护作用。4.有关胃粘液分泌的药物评价。建立了一种连续测定胃粘液分泌的方法。5.阐明胃酸分泌的神经调控机制。研究了药物对胃分泌的中枢刺激作用。谷氨酸相关化合物的刺激作用被证明，这将是非常有趣的相关应激性溃疡。6.抗溃疡活性的药物评价。研究了酵母提取物、小檗碱及其相关化合物和甘草次酸类似物的抗溃疡活性。在未来的研究中，将特别参考它们的神经和局部调节来阐明胃粘膜防御机制。较少

Studies on gastric mucosal defensive mechanisms and their related drug action were conducted. Results obtained were as follow: 1. Drug Evaluation concerning Gastric Mucosal Defensive Functions. Gastric mucosal damage was produced by hemorrhagic shock or administration of platelet activating factor (PAF). The drug tests (prostaglandins, autonomic drugs, azulene compounds) suggest that autonomic factors and generation of superoxides are relevant to features of the former model, while vascular factors are closely involved in features of the latter model. Inflammatory responses were probably associated with PAF-induced gastric damage. Furthermore, a method for drug evaluation related to defensive mechanisms was established by measuring gastric potential difference (PD). Gastric PD was very susceptible to factors or substances damaging gastric mucosa. Using this method, the effectiveness of carbenoxolone and ammonia-induced mucosal irritation were apparently demonstrated. 2. Drug Evaluation … More concerning Gastric Blood Flow. A method for isolated perfused whole stomach preparation was established. Using this method, endothelin was found to potently and continuously produce a vaso- constriction. On the other hand, one of azulene compounds showed an increase in gastric blood flow in anesthetized rats. 3. Drug Evaluation concerning Cytoprotective Action. The release from intracellular enzymes by ethanol damaging was measured both in isolated suspended gastric mucosal cells and in gastric mucosa of anesthetized rats. Carbenoxolone exerted a cytoprotective action in the both methods. 4. Drug Evaluation concerning Gastric Mucus Secretion. A method for consecutively measuring gastric mucus secretion was established. 5. Elucidation of Neural Control in Gastric Acid Secretion. Centrally stimulating action of drugs on gastric secretion was studied. Stimulatory actions of glutamic acid related compounds were demonstrated, which would be very interesting in association with stress ulceration. 6. Drug Evaluation of Antiulcer Activities. Antiulcer activities of yeast extracts, berbeline and its related compounds, and glycyrrhetinic acid analogs were examined.In future studies, gastric mucosal defensive mechanisms will be clarified in special reference to their neural and local regulation. Less