• Modeling Mechanism：

  Histamine dihydrochloride needs to act synergistically with indomethacin to induce a rat model of duodenal ulcer. It strongly promotes gastric acid secretion by binding to H₂ receptors on parietal cells, and synergizes with indomethacin to inhibit duodenal bicarbonate secretion and weaken mucosal defense function, resulting in a sharp increase in acid load in the duodenum, damage to mucosal epithelial cells, and ultimately ulcer formation.

• Related Products：

  Histamine (T0965)

• Modeling Method：

  Experimental Subject：

  Rats, Donryu, Male, Body weight 230-260g, Fasted for 24 hours

  Dosage and Administration Route：

  ① Core modeling: Indomethacin (5 mg/kg) suspended in saline with a trace of Tween 80 via subcutaneous injection (0.5 ml/100g body weight); 30 minutes later, histamine dihydrochloride (40 mg/kg) dissolved in 10% gelatin via subcutaneous injection, 3 doses total with 2.5-hour intervals between doses;
  ② Control treatment: Single subcutaneous injection of indomethacin (5 mg/kg) alone, histamine (40 mg/kg, 3 doses with 2.5-hour intervals) alone, or isovolumetric vehicle (saline with Tween 80/10% gelatin);
  ③ Intervention validation (optional): Cimetidine (3-100 mg/kg) suspended in saline via oral gavage; 16,16-dimethylprostaglandin E₂ (dmPGE₂, 3-30 μg/kg) first dissolved in absolute ethanol then diluted with saline via oral gavage; both administered 30 minutes prior to indomethacin injection

  Dosing Frequency and Duration Model：

  Single indomethacin injection+3 histamine injections (2.5-hour intervals)

• Validation：

  1. Pathological indicators: 1-2 round ulcer lesions (area 9.8±1.4 mm²) in the proximal duodenum with 100% ulcer incidence; a few scattered lesions in the gastric corpus and antrum; 30%-40% of duodenal ulcers penetrated the muscularis mucosae, and a single large round ulcer was still visible after 32 hours; no ulcer formation with indomethacin or histamine alone; 2. Biochemical indicators: Gastric acid secretion significantly increased compared with the control group (peak value 23-25 μEq/15 min for histamine alone, >30 μEq/15 min for combined administration); duodenal basal HCO₃⁻ secretion slightly inhibited, and acid-stimulated HCO₃⁻ secretion completely blocked; 3. Drug intervention validation: Cimetidine (≥10 mg/kg) dose-dependently inhibited ulcer formation and significantly reduced gastric acid secretion; dmPGE₂ (3-30 μg/kg) dose-dependently reduced the area of duodenal and antral ulcers and significantly increased HCO₃⁻ secretion; both reduced the acid load in the duodenum (peak value 24.2±1.6 μEq/30 min in the cimetidine group, 35.1±4.8 μEq/30 min in the dmPGE₂ group).

*Precautions： Subjects were euthanized and sampled 8 hours after indomethacin administration; some animals were normally fed for 24 hours after the last histamine injection and sampled 32 hours after indomethacin administration.

*References：Takeuchi K,et,al. A new model of duodenal ulcers induced in rats by indomethacin plus histamine. Gastroenterology. 1986 Mar;90(3):636-45.