Navarová J, Nosálová V
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Methods Find Exp Clin Pharmacol. 1994 Mar;16(2):119-24.
The in vivo effect of indomethacin and three H2-receptor antagonists-cimetidine, ranitidine, and famotidine-on gastric damage and on the activity of lysosomal enzymes and on proteins was examined in rat gastric mucosa and serum. The activities of the lysosomal enzymes N-acetyl-beta-glucosaminidase (NAGA), acid phosphatase (APh), and beta-D-glucuronidase (GLU) decreased significantly in gastric mucosa 2, 4, 6 and 12 h after subcutaneous administration of indomethacin (20 mg/kg). The serum activities of the lysosomal enzymes were unchanged. A decrease of protein in gastric mucosa was observed 4 and 6 h after indomethacin administration. Pretreatment with cimetidine and ranitidine reduced dose-dependently the length of gastric lesions induced by indomethacin, as well as the decrease in lysosomal enzyme mucosal activities. Famotidine, in spite of its antiulcer effect, failed to prevent the release of NAGA and APh, yet proved to inhibit GLU release. The results suggest that, in addition to their gastroprotective effect, H2-receptor antagonists may contribute to lysosomal membrane protection in indomethacin-induced gastric injury.
在大鼠胃黏膜和血清中检测了吲哚美辛及三种H2受体拮抗剂——西咪替丁、雷尼替丁和法莫替丁——对胃损伤、溶酶体酶活性及蛋白质的体内作用。皮下注射吲哚美辛（20 mg/kg）后2、4、6和12小时，胃黏膜中溶酶体酶N-乙酰-β-氨基葡萄糖苷酶（NAGA）、酸性磷酸酶（APh）和β-D-葡萄糖醛酸酶（GLU）的活性显著降低。溶酶体酶的血清活性未发生变化。吲哚美辛给药后4和6小时观察到胃黏膜中蛋白质减少。西咪替丁和雷尼替丁预处理可剂量依赖性地减少吲哚美辛诱导的胃损伤长度，以及溶酶体酶黏膜活性的降低。尽管法莫替丁具有抗溃疡作用，但未能阻止NAGA和APh的释放，但证明可抑制GLU的释放。结果表明，除了具有胃保护作用外，H2受体拮抗剂可能有助于在吲哚美辛诱导的胃损伤中保护溶酶体膜。
