Ko J K, Cho C H, Ogle C W
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
J Gastroenterol Hepatol. 1994 Sep-Oct;9(5):492-500. doi: 10.1111/j.1440-1746.1994.tb01280.x.
The protective effect of mild irritants against the subsequent gastric injury induced by necrotizing agents has been termed 'adaptive cytoprotection'. In this study, the possible pathway and mechanisms of adaptive cytoprotection induced by 20% ethanol were investigated. An ex-vivo gastric chamber preparation was used. The gastric mucosa was exposed to 20% ethanol before subsequent administration of 100% ethanol 15 min later. Subdiaphragmatic vagotomy or drug pretreatment was carried out in order to elucidate the mechanisms of adaptive cytoprotection by 20% ethanol. The results showed that 20% ethanol pre-exposure significantly protected the gastric mucosa against damage caused by 100% ethanol. This protective action was completely abolished by atropine or lidocaine pretreatment, whereas vagotomy and hexamethonium failed to have a significant influence. The cytoprotective effect, however, was independent of the gastric secretory volume, titratable acid content, luminal soluble mucus level and gastric mucosal blood flow. Exposure of only half the gastric mucosa to the mild irritant resulted in the protection of both sides of the mucosa. All these findings indicate that the adaptive cytoprotection of 20% ethanol involves the participation of chemoreceptors and muscarinic receptors in the gastric mucosa. An internal enteric reflex arc, with transmission of signals within the gastric mucosa, may also contribute to the cytoprotective process of the mild irritant.
轻度刺激物对随后由坏死剂引起的胃损伤的保护作用被称为“适应性细胞保护”。在本研究中,对20%乙醇诱导的适应性细胞保护的可能途径和机制进行了研究。采用离体胃腔制备方法。在随后15分钟给予100%乙醇之前,先将胃黏膜暴露于20%乙醇中。进行膈下迷走神经切断术或药物预处理,以阐明20%乙醇适应性细胞保护的机制。结果表明,预先暴露于20%乙醇可显著保护胃黏膜免受100%乙醇造成的损伤。阿托品或利多卡因预处理可完全消除这种保护作用,而迷走神经切断术和六甲铵则没有显著影响。然而,细胞保护作用与胃分泌量、可滴定酸含量、腔内可溶性黏液水平和胃黏膜血流量无关。仅将一半的胃黏膜暴露于轻度刺激物下,可使黏膜两侧均得到保护。所有这些发现表明,20%乙醇的适应性细胞保护涉及胃黏膜中化学感受器和毒蕈碱受体的参与。胃黏膜内信号传递的内在肠反射弧也可能有助于轻度刺激物的细胞保护过程。