Takeuchi K, Okada M, Ueshima K, Ohuchi T, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Digestion. 1993;54(2):91-7. doi: 10.1159/000201019.
The role of endogenous sulfhydryls (SH) in the healing of HCl-induced gastric injury was investigated in the rat. The animals fasted for 18 h were given 1 ml of 0.6 N HCl by gavage, and they were fed normally from 1 h later and killed various days after HCl treatment. Gastric lesions induced by HCl healed to quiescent states within 7 days both macroscopically and histologically. Mucosal SH levels were markedly reduced after induction of damage by HCl, but recovered gradually to or above normal values within 5 days. Gastric acidity was also significantly reduced after administration of 0.6 N HCl (induction of lesions), followed by a return to normal values within 5 days, although the volume of gastric contents remained unchanged before and after HCl treatment. The healing of HCl-induced gastric lesions was significantly impaired by diethylmaleate (DEM 0.3 ml/kg x 2) when this drug was given subcutaneously for 5 days. Glutathione (GSH: 100 mg/kg x 2) alone did not affect the healing of gastric lesions, but the combined administration of GSH with DEM significantly antagonized the delayed healing caused by DEM. Administration of DEM caused a marked and persistent reduction in the mucosal SH contents, while GSH by itself significantly increased the mucosal SH levels and partially reversed the reduced SH contents caused by DEM. Gastric acid secretion was not significantly altered by either DEM or GHS. These results suggest that endogenous SH may play some roles in the healing process of gastric mucosal lesions. DEM caused a deleterious effect on the healing of gastric lesions, probably by reducing the mucosal SH.
研究了内源性巯基（SH）在大鼠盐酸诱导的胃损伤愈合中的作用。将禁食18小时的动物经口灌胃给予1 ml 0.6 N盐酸，1小时后正常喂食，并在盐酸处理后的不同天数处死。盐酸诱导的胃损伤在7天内无论在宏观还是组织学上均愈合至静止状态。盐酸诱导损伤后黏膜SH水平显著降低，但在5天内逐渐恢复至正常水平或高于正常水平。给予0.6 N盐酸（诱导损伤）后胃酸也显著降低，随后在5天内恢复至正常水平，尽管盐酸处理前后胃内容物体积不变。当皮下注射二乙基马来酸酯（DEM 0.3 ml/kg×2）5天时，盐酸诱导的胃损伤愈合明显受损。单独给予谷胱甘肽（GSH：100 mg/kg×2）不影响胃损伤的愈合，但GSH与DEM联合给药可显著拮抗DEM引起的愈合延迟。给予DEM导致黏膜SH含量显著且持续降低，而GSH本身可显著提高黏膜SH水平，并部分逆转DEM导致的SH含量降低。DEM或GHS均未显著改变胃酸分泌。这些结果表明内源性SH可能在胃黏膜损伤的愈合过程中发挥某些作用。DEM对胃损伤的愈合产生有害影响，可能是通过降低黏膜SH实现的。
