Ligumsky M, Sestieri M, Karmeli F, Rachmilewitz D
Isr J Med Sci. 1986 Nov;22(11):807-11.
"Mild irritants" have been shown to protect rat gastric mucosa from damage induced by noxious topical agents, supposedly by induction of mucosal prostaglandin (PG) biosynthesis. The protective effect of NaCl 5%, ethanol 20%, NaOH 0.075 N, HCl 0.35 N, salicylic acid 100 mg/kg and paracetamol 200 mg/kg was investigated in rats treated with an ulcerogenic dose (25 mg/kg) of indomethacin; mucosal PG synthesis was simultaneously determined. Significant protection was achieved only with NaCl 5%, salicylic acid and paracetamol. Salicylic acid and paracetamol significantly decreased acid secretion and enhanced PGE2 or 6-keto PGF1 alpha generation in control rats, while a small but significant change in the indomethacin-inhibited PG synthesis was observed after treatment with NaCl 5% or salicylic acid. We conclude that protection by "mild irritants" against indomethacin-induced mucosal damage may involve increased cytoprotective PG generation, as shown for paracetamol and salicylic acid, or partial blocking of indomethacin binding at the cyclooxygenase receptor site, as shown for NaCl 5% and salicylic acid.
“轻度刺激物”已被证明可保护大鼠胃黏膜免受有害局部药物诱导的损伤，推测是通过诱导黏膜前列腺素（PG）生物合成实现的。研究了5%氯化钠、20%乙醇、0.075N氢氧化钠、0.35N盐酸、100mg/kg水杨酸和200mg/kg对乙酰氨基酚对用致溃疡剂量（25mg/kg）吲哚美辛处理的大鼠的保护作用；同时测定黏膜PG合成。仅5%氯化钠、水杨酸和对乙酰氨基酚具有显著保护作用。水杨酸和对乙酰氨基酚显著降低对照大鼠的胃酸分泌并增强PGE2或6-酮-PGF1α的生成，而在用5%氯化钠或水杨酸处理后，观察到吲哚美辛抑制的PG合成有小但显著的变化。我们得出结论，“轻度刺激物”对吲哚美辛诱导的黏膜损伤的保护作用可能涉及增加细胞保护性PG的生成，如对乙酰氨基酚和水杨酸所示，或部分阻断吲哚美辛在环氧化酶受体位点的结合，如5%氯化钠和水杨酸所示。
