Takeuchi K, Okada M, Niida H, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Dig Dis Sci. 1991 Jul;36(7):870-9. doi: 10.1007/BF01297134.
The effects of N-ethylmaleimide (NEM), a sulfhydryl (SH) blocker, on ethanol-induced gastric lesions were investigated in rats by varying the route of administration. Oral administration of acidified ethanol (60% ethanol in 150 mM HCl, 1 ml) produced hemorrhagic bandlike lesions in the gastric mucosa. Pretreatment of the animals with orally administered NEM (0.1-10 mg/kg) dose-dependently inhibited these lesions (the inhibition was over 80% at 1 mg/kg or greater), and the effects were partially reversed by indomethacin (5 mg/kg, subcutaneous). However, when NEM (10 mg/kg) was given subcutaneously, this agent significantly worsened the lesions. Intragastrically applied NEM produced a dose-dependent reduction of the transmucosal potential difference (PD) and the mucosal nonprotein SH levels, an increase of the volume of gastric contents, and an inhibition of gastric motility, while these parameters remained unaltered after subcutaneous administration of the agent. The microvascular permeability in the mucosa was significantly increased by both oral and subcutaneous administration of NEM (10 mg/kg) but remained unchanged in response to lower doses of orally administered (less than 3 mg/kg). These results suggest that NEM given orally is cytoprotective to the stomach against ethanol, probably by acting as a mild irritant and due to dilution of an irritant and inhibition of gastric motility (muscle relaxation), but when given subcutaneously it aggravates the lesions by unknown mechanisms.
通过改变给药途径，研究了巯基（SH）阻断剂N - 乙基马来酰亚胺（NEM）对乙醇诱导的大鼠胃损伤的影响。口服酸化乙醇（150 mM HCl中60%乙醇，1 ml）可在胃黏膜产生出血带状损伤。给动物口服NEM（0.1 - 10 mg/kg）预处理可剂量依赖性抑制这些损伤（1 mg/kg及以上时抑制率超过80%），吲哚美辛（5 mg/kg，皮下注射）可部分逆转这些作用。然而，当皮下注射NEM（10 mg/kg）时，该药物会显著加重损伤。胃内应用NEM会导致跨黏膜电位差（PD）和黏膜非蛋白SH水平呈剂量依赖性降低，胃内容物体积增加，胃动力受到抑制，而皮下注射该药物后这些参数保持不变。口服和皮下注射NEM（10 mg/kg）均会使黏膜微血管通透性显著增加，但口服较低剂量（小于3 mg/kg）时则无变化。这些结果表明，口服NEM可能通过作为轻度刺激物、稀释刺激物和抑制胃动力（肌肉松弛）对胃起到抗乙醇细胞保护作用，但皮下注射时会通过未知机制加重损伤。
