Bedekovic Vlado, Mise Stjepan, Anic Tomislav, Staresinic Mario, Gjurasin Miroslav, Kopljar Mario, Kalogjera Livije, Drvis Petar, Boban Blagaic Alenka, Batelja Lovorka, Seiwerth Sven, Sikiric Predrag
Department of Pharmacology, Medical Faculty University of Zagreb, Salata 11, POB916, 10000 Zagreb, Croatia.
Eur J Pharmacol. 2003 Sep 5;477(1):73-80. doi: 10.1016/j.ejphar.2003.08.013.
The focus was on salivary glands in cysteamine-induced duodenal ulcer and the different effects of antiulcer agents on cysteamine-induced duodenal ulcer in sialoadenectomized but not gastrectomized rats. We tested antiulcer agents on cysteamine-induced duodenal ulcer in rats (agents/kg i.p.) simultaneously with cysteamine 400 mg/kg s.c., rat killed 24 h thereafter subjected to no surgery (normal), to gastrectomy (24 h before) or sialoadenectomy, acute (24 h before) or chronic (21 days before). (i) Ulcerogenesis: cysteamine-induced duodenal ulcer had the same severity and incidence in normal, gastrectomized or acutely or chronically sialoadenectomized rats. (ii) Antiulcer effect under normal conditions or following gastrectomy: in normal or gastrectomized rats all agents tested, gastric pentadecapeptide BPC 157 [currently in clinical trials for inflammatory bowel disease (PL-10, PLD-116, PL-14736, Pliva) (10.0 microg or 10.0 ng), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg)] inhibited cysteamine-induced duodenal ulcers, acting through gastric acid-independent mechanisms. Following sialoadenectomy, acute or chronic: ranitidine, omeprazole and atropine were completely ineffective, while pentadecapeptide BPC 157 could protect. Thus, we found that contrary to stomach, salivary glands are implicated in cytoprotective agent activity (standard agents were ineffective after sialoadenectomy). Also, gastric pentadecapeptide BPC 157 was consistently associated with a cytoprotective effect, suggesting a beneficial activity distinctive from that of H2-receptor blockers, proton-pump inhibitors and anticholinergics; but probably replacing missing salivary glands factors.
研究重点为半胱胺诱导的十二指肠溃疡中的唾液腺，以及抗溃疡药物对唾液腺切除但未行胃切除的大鼠半胱胺诱导的十二指肠溃疡的不同影响。我们在大鼠半胱胺诱导的十二指肠溃疡模型上测试抗溃疡药物（腹腔注射，药物剂量/千克），同时皮下注射400毫克/千克半胱胺，24小时后处死大鼠，大鼠未接受任何手术（正常组）、接受胃切除术（术前24小时）或唾液腺切除术，急性唾液腺切除术（术前24小时）或慢性唾液腺切除术（术前21天）。（i）溃疡形成：半胱胺诱导的十二指肠溃疡在正常、胃切除、急性或慢性唾液腺切除的大鼠中严重程度和发生率相同。（ii）正常条件下或胃切除后的抗溃疡作用：在正常或胃切除的大鼠中，所有测试药物，胃十五肽BPC 157 [目前正在进行炎症性肠病的临床试验（PL - 10、PLD - 116、PL - 14736、普利瓦）（10.0微克或10.0纳克）]、雷尼替丁（10毫克）、阿托品（10毫克）、奥美拉唑（10毫克）均通过非胃酸依赖机制抑制半胱胺诱导的十二指肠溃疡。在急性或慢性唾液腺切除后：雷尼替丁、奥美拉唑和阿托品完全无效，而十五肽BPC 157具有保护作用。因此，我们发现与胃不同，唾液腺与细胞保护剂活性有关（唾液腺切除后标准药物无效）。此外，胃十五肽BPC 157始终具有细胞保护作用，表明其具有与H2受体阻滞剂、质子泵抑制剂和抗胆碱能药物不同的有益活性；但可能替代了缺失的唾液腺因子。
