[Animal modeling - Drug efficacy evaluation] - Water immersion restraint method induced stress-induced gastric ulcer animal model

  (1) Method of replication: Adult rats were fasted without water for 24 hours, anesthetized with ether, and placed in a supine position. The animal's limbs and neck were tied and fixed onto a mouse plate. After waking up, immerse in a constant temperature water bath at 20-23 ℃, keeping the water level at the sternum xiphoid process level, and soak for 20-24 hours. After soaking, remove the animal, dry the skin, euthanize by bleeding, and immediately perform a post-mortem examination. First, ligate the pylorus with a thread, then use a syringe to draw 10ml of 10% formaldehyde solution, inject it into the stomach through the esophagus, and remove the needle to ligate the cardia. Cut off the esophagus and duodenum at both ends of the two ligatures, and remove the entire stomach. Wait for 30 minutes, cut open along the large bend, flatten, rinse with isotonic saline, and visually observe the damage to the gastric mucosa. The degree of injury is expressed by the injury index: 1 point for point injuries, 2 points for injuries less than 1mm, 3 points for injuries 1-2mm, 4 points for injuries 2-4mm, 5 points for injuries greater than 4mm. When the lesion width is 2mm, the score is multiplied by 2. The total score of gastric mucosal injury index is the sum of all injury scores of each animal's gastric mucosa.

  (2) The characteristics of the model are that after being immersed in water for 3 hours, the gastric mucosa begins to develop ulcers. At 7-8 hours, multiple and hemorrhagic erosion spots appear on the gastric mucosa. After 20 hours, the lesions of the gastric mucosa worsen, but the lesions do not exceed the mucosal muscle layer, and are mainly in the glandular stomach. The lesion site is usually distributed along the blood vessels, and the surface is covered with coagulation. After wiping off the coagulation, dark brown linear ulcers can be seen.

  (3) Comparative medicine stress ulcer refers to an acute stress response that occurs in the body when it is hit by a major emergency event. When the body encounters sudden events such as severe trauma, severe illness, severe mental stimulation, and psychological disorders, the excitability of its sympathetic nervous system and parasympathetic pituitary adrenal system immediately increases. The former causes gastric vascular constriction, insufficient gastric mucosal blood flow, cellular energy metabolism disorders, and decreased mucosal barrier function, while the latter promotes increased secretion of gastric acid, pepsin, and gastrin, leading to the occurrence of stress ulcers. At present, there are various animal models of acute gastric mucosal lesions established according to the above principles, mainly including: mouse, rat, guinea pig restraint immersion method, rat hot water burn method, rabbit femur comminuted fracture method, exhaustion exercise method, etc. Due to the developed function of the rat adrenal system and its sensitivity to stress response, it is often used as a modeling object to replicate animal models of stress-induced gastric ulcers. The rat model replicated by water immersion constraint method usually shows coffee colored bleeding points and focal mucosal defects in the glandular stomach, with a depth not exceeding the muscle layer. The ulcer index can generally be determined by the total length of the ulcers in millimeters. In the process of replicating the model, attention should be paid to and adjusted for the possible impact of factors such as water temperature, animal species, gender, and weight on the degree of mucosal pathological damage. The biggest feature of this model is its simple replication method, high modeling success rate (up to 100%), good experimental reproducibility, and similarity to the natural development process of human stress-induced gastric ulcers. Anticholinergic drugs and central inhibitory drugs can reduce their incidence, making it a common experimental model in the field of anti gastric ulcer drug research and one of the main models for screening anti psychosomatic disease drugs in modern medical research.