Dupuy D, Szabo S
Gastroenterology. 1986 Oct;91(4):966-74. doi: 10.1016/0016-5085(86)90701-8.
Recent evidence suggests a role of endogenous sulfhydryls (SHs) in gastric "cytoprotection." Because divalent metals bind to or oxidize SH groups, their effect on ethanol-induced gastric erosions was studied. For comparative biochemical studies the SH cysteamine, the glutathione depletor diethylmaleate. and SH alkylating agent N-ethylmaleimide (NEM) were also used. Rats pretreated with CdCl2, ZnCl2, or Cu(NO3)2 6 h before absolute ethanol showed a significant dose-dependent decrease in the mucosal lesions. Copper was effective in preventing the lesions up to 15 min before the ethanol. Iron and manganese were active at 30 min, but not at 6 h before the ethanol lesions. Indomethacin administration decreased the protection afforded by iron, manganese, and cadmium, but did not modify that by lead and copper. N-ethylmaleimide abolished the protection by iron, manganese, and cadmium, but did not affect the protection caused by lead and copper when given after the metals. However, when NEM was given before lead and copper, it diminished the protection. Secretory studies revealed that cadmium and zinc slightly inhibited gastric acid secretion, but a similar reduction of acid output by cimetidine did not decrease the ethanol-induced gastric erosions. Biochemical studies of endogenous SH showed that the protective metals and NEM decreased the glutathione concentration in the nonprotein fraction, whereas these metals diminished and NEM, which antagonizes mucosal protection, elevated the cysteine concentration in the protein fraction of the gastric mucosa. The common factor with the protective agents thus seems to be the blocking of protein SH by binding or oxidation by protective agents. These endogenous SHs may mediate cellular responses to injury.
最近的证据表明内源性巯基（SHs）在胃“细胞保护”中发挥作用。由于二价金属会与SH基团结合或使其氧化，因此研究了它们对乙醇诱导的胃糜烂的影响。为了进行比较生化研究，还使用了SH半胱胺、谷胱甘肽耗竭剂马来酸二乙酯以及SH烷基化剂N-乙基马来酰亚胺（NEM）。在给予无水乙醇前6小时用CdCl2、ZnCl2或Cu(NO3)2预处理的大鼠，其黏膜损伤呈显著的剂量依赖性降低。铜在乙醇注射前15分钟内均能有效预防损伤。铁和锰在乙醇损伤前30分钟有活性，但在6小时时无活性。给予吲哚美辛会降低铁、锰和镉提供的保护作用，但不会改变铅和铜提供的保护作用。N-乙基马来酰亚胺消除了铁、锰和镉的保护作用，但在金属给药后给予时，并不影响铅和铜引起的保护作用。然而，当在铅和铜之前给予NEM时，它会减弱保护作用。分泌研究表明，镉和锌会轻微抑制胃酸分泌，但西咪替丁引起的类似酸分泌减少并未降低乙醇诱导的胃糜烂。内源性SH的生化研究表明，具有保护作用的金属和NEM会降低非蛋白部分中的谷胱甘肽浓度，而这些金属会降低且拮抗黏膜保护作用的NEM会升高胃黏膜蛋白部分中的半胱氨酸浓度。因此，保护剂的共同因素似乎是通过结合或氧化来阻断蛋白质SH。这些内源性SHs可能介导细胞对损伤的反应。
