Warzecha Z, Dembiński A, Brzozowski T, Ceranowicz P, Pajdo R, Niemiec J, Drozdowicz D, Mitis-Musioł M, Konturek S J
Dept. of Physiology, Collegium Medicum of Jagiellonian University, Cracow, Poland.
Scand J Gastroenterol. 2000 Sep;35(9):916-24. doi: 10.1080/003655200750022959.
Previous studies have shown that ammonia produced by Helicobacter pylori urease or administrated intragastrically exhibits a toxic effect on the gastric mucosa. In the present study we investigated the influence of histamine and gastric acid secretion on ammonia (NH4OH)-induced gastric lesions.
The gastric mucosa in rats was exposed to NH4OH (1.5 ml of 250 mM solution) under basal conditions, after administration of histamine (1 mg/kg), urea with urease, and ranitidine (40 mg/kg subcutaneously) given alone or in combination. We measured the area of gastric lesions, gastric blood flow (GBF), plasma gastrin concentration, DNA synthesis, gastric acid secretion and gastric luminal concentration of PGE2.
Application of NH4OH resulted in the formation of acute gastric lesions. This effect was accompanied by a fall in GBF, a rise in gastric pH, and a reduction in mucosal DNA synthesis. Administration of histamine 30 min prior to NH4OH reduced the area of gastric lesions. This was accompanied by an increase in GBF, DNA synthesis, and prostaglandin E2 (PGE2) production. Ranitidine given prior to NH4OH enhanced gastric mucosa damage, and reduced GBF and DNA synthesis. This effect was accompanied by a reduction in gastric acid secretion. Ranitidine given prior to histamine abolished gastric acid secretion and the protective effect of histamine against NH4OH-induced damage; these effects were accompanied by a decrease in GBF, DNA synthesis, and concentration of PGE2. Pretreatment with 2% urea with urease given prior to NH4OH reduced NH4OH lesions. This effect was associated with an increase in gastric acid secretion, gastric generation of PGE2, GBF, and DNA synthesis. Ranitidine given prior to urea with urease inhibited gastric acid secretion and the gastroprotective effect of urea-urease gastroprotection.
Histamine and gastric secretion exhibit a protective effect against ammonia-induced gastric lesions. This effect appears to depend upon the stimulation of gastric acid secretion and PGE2 production, and the improvement of gastric microcirculation.
先前的研究表明，幽门螺杆菌脲酶产生的氨或胃内给予的氨对胃黏膜具有毒性作用。在本研究中，我们调查了组胺和胃酸分泌对氨（NH₄OH）诱导的胃损伤的影响。
在基础条件下，以及单独或联合给予组胺（1 mg/kg）、尿素与脲酶、雷尼替丁（40 mg/kg皮下注射）后，将大鼠胃黏膜暴露于NH₄OH（250 mM溶液1.5 ml）。我们测量了胃损伤面积、胃血流量（GBF）、血浆胃泌素浓度、DNA合成、胃酸分泌以及胃腔内PGE₂浓度。
应用NH₄OH导致急性胃损伤的形成。这种效应伴随着GBF下降、胃pH值升高以及黏膜DNA合成减少。在给予NH₄OH前30分钟给予组胺可减少胃损伤面积。这伴随着GBF、DNA合成以及前列腺素E₂（PGE₂）产生增加。在给予NH₄OH前给予雷尼替丁会加重胃黏膜损伤，并降低GBF和DNA合成。这种效应伴随着胃酸分泌减少。在给予组胺前给予雷尼替丁可消除胃酸分泌以及组胺对NH₄OH诱导损伤的保护作用；这些效应伴随着GBF、DNA合成以及PGE₂浓度降低。在给予NH₄OH前用2%尿素与脲酶预处理可减少NH₄OH损伤。这种效应与胃酸分泌增加、胃内PGE₂产生、GBF以及DNA合成增加有关。在给予尿素与脲酶前给予雷尼替丁可抑制胃酸分泌以及尿素-脲酶胃保护的胃保护作用。
组胺和胃酸分泌对氨诱导的胃损伤具有保护作用。这种作用似乎取决于胃酸分泌和PGE₂产生的刺激以及胃微循环的改善。
