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

胃粘膜防御机制及药物细胞保护作用分析的药理学研究

• 批准号: 63571033
• 负责人: YANO Shingo
• 金额: $ 1.34万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63571033/
• 关键词: Gastric Mucosal Defensive Mechanism; Drug Evaluation; Antiulcer Drug; Cytoprotective Action; Gastric Acid Secretion; Gastric Blood Flow; Gastric Ulcer; Gastric Mucosal Potential Difference; 抗潰瘍薬; 胃潰瘍; 胃粘液分泌; 胃粘膜電位

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

对胃粘膜防御机制及其相关药物作用进行了研究。主要研究结果如下：1.关于胃粘膜防御功能的药物评价。失血性休克或血小板活化因子（PAF）引起胃粘膜损伤。药物测试（植物药，植物性药物，甘菊烯化合物）表明，植物性因素和超氧化物的产生与前一种模型的特征有关，而血管因素密切参与后一种模型的特征。炎症反应可能与PAF引起的胃损伤有关。此外，通过测量胃电位差（PD），建立了与防御机制相关的药物评价方法。胃PD易受胃粘膜损伤因素或物质的影响。使用这种方法，有效性的甘珀酸和氨诱导的粘膜刺激明显证明。2.药品审评 ...更多信息 关于胃血流量。建立了离体灌流全胃制备方法。使用这种方法，内皮素被发现有效地和连续地产生血管收缩。另一方面，在麻醉大鼠中，一种甘菊环化合物显示胃血流量增加。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胃粘膜中测量乙醇损伤引起的细胞内酶的释放。甘珀酸在这两种方法中都具有细胞保护作用。4.关于胃粘液分泌的药物评价。建立了连续测定胃粘液分泌的方法。5.阐明胃酸分泌的神经控制。研究了药物对胃分泌的中枢兴奋作用。谷氨酸相关化合物的刺激作用被证明，这将是非常有趣的与应激性溃疡。6.抗溃疡活性的药物评价。本研究检测了酵母提取物、小檗碱及其相关化合物和大黄酸类似物的抗胃溃疡活性，在未来的研究中，将特别参考其神经和局部调节阐明胃粘膜防御机制。少

项目成果

K.Yogo: "Vasoconstrictor effect of endothelin in isolated perfused stomach of the rat in comparison with noradrenaline and serotonin." Japan.J.Pharmacol.52. 160-163 (1990)

K.Yogo：“与去甲肾上腺素和血清素相比，内皮素在大鼠离体灌注胃中的血管收缩作用。”

S.YANO: "Stimulatory effect of some therapeutic drugs used for improving cerebral insufficiency on gastric acie secretion in rats." Pharmacology. (1990)

S.YANO：“一些用于改善脑供血不足的治疗药物对大鼠胃酸分泌的刺激作用。”

Wen^chuan,Lin: Jpn.J.Pharmacol.49. 267-274 (1989)

林文^川：Jpn.J.Pharmacol.49。

K. HATAKEYAMA: "Platelet activating factor (PAF)-induced gastric damage in rats: Participation of increased gastric vascular permeability." Scand. J. Gastroenterol., 24 (Supple. 162), 71-74 (1989).

K. HATAKEYAMA：“血小板激活因子 (PAF) 诱导的大鼠胃损伤：胃血管通透性增加的参与。”

S. YANO: "Stimulatory effect of some therapeutic drugs used for improving cerebral insufficiency on gastric acid secretion in rats." Pharmacology (1990).

S. YANO：“一些用于改善脑供血不足的治疗药物对大鼠胃酸分泌的刺激作用。”