Method for modeling stomach and intestine ulceration

FIELD: medicine.

SUBSTANCE: method involves intragastrically introducing indometacin to rats at a dose of 4.5-5 mg/kg of mass after holding the animals without food and water during 5 days.

EFFECT: enhanced effectiveness of bleeding and perforating ulcer formation.

2 tbl

 

The invention relates to medicine, namely to provide a method for modeling ulcerative lesions of the gastrointestinal tract, and can be used for the experimental study of the process of ulcer formation in the lining of the stomach and intestine, induced by the use of nonsteroidal anti-inflammatory drugs, as well as to search for new means of prevention and treatment of ulcerogenesis.

Known modeling ulcerative lesions of the stomach through the abdominal cavity of rats indomethacin at a dose of 25-30 mg/kg once (Sarnow L.N., Hazura CENTURIES "Elements of experimental pharmakologie". - M, 2000 - s.219).

However, this model does not reflect the full extent pathophysiological mechanisms damaging effect of nonsteroidal anti-inflammatory drugs on the mucous membrane with a long reception and based on single acute toxicity leading to death of part of the experimental animals.

The technical result consists in creating the most physiological model of ulcerative lesions of the gastrointestinal tract, as close as possible to that of persons receiving long-term nonsteroidal anti-inflammatory drugs.

The invention consists in that the method of modeling ulcerative lesions of the stomach and intestines is carried out by introducing the animal is indomethacin at a dose of 4.5-5 mg/kg intragastrically after two hours without food and water daily for 5 days.

The method is as follows. Take outbred rats of both sexes weighing 180-210 g Rats injected with indomethacin at a dose of 4.5 and 5 mg/kg intragastrically after two hours without food and water daily for 5 days. On the 6th day was carried out the slaughter of animals by the method of decapetala. At autopsy was estimated pattern of the mucous membrane of the stomach and intestines: the number and size of ulcers, signs of stomach bleeding, perforation of the intestinal wall, the ratio of deep and superficial ulceration.

Example 1. Course administration of indomethacin at a dose of 5 mg/kg had ulcerogenic action on the mucous membrane of the stomach in 100% of cases. Half of the animals revealed signs intragastric bleeding. The membranous part of the stomach was rapidly become thin, mucous membrane muscle part became loose. Ulcerative defect was localized in both parts, their sizes ranged from 0.1×0.1 to 4×9 mm While 78,9% of all ulcers were presented deep ulcers, and their area was 92.0% of the total area of the ulcer surface (table 1).

The total number of ulcers was 12.0±0,8 per animal, the number of deep ulcers - 9,60±0,67, surface - 2,40±0,60. The area of ulcerative lesions on the background of the introduction of indometacin reached one-21.32±3,83 mm2area opertion is such defects 19,38±and 3.72 mm2surface - 1,94±0.47 mm2on one animal.

The infusion of 5 mg/kg indomethacin probe method in the intestinal mucosa in all animals was the formation of ulcers of varying depth. Mainly ulceration occurred in the distal small intestine for 45-55 cm and in the colon. In the small intestine ulcers had dimensions of 1×1 and 3×5 mm, number of ulcers from 2 to 8 on 1 cm2. In 60% of animals ulcers were performable intestinal wall. The small intestine was distended, the wall is thinned to transparency. In three animals at necropsy signs of peritonitis in peritoneal cavity detected 3-3,5 ml of turbid yellowish-hemorrhagic fluid. The rest of the stomach and bowel loops were allocated poorly. In the colon was observed multiple defects to the muscle layer. Often they wore the drain nature, places a continuous layer covered the inner surface of the intestine.

The number of ulcers in the small intestine 1 animal was 3,80±0,64 on 1 cm2(just 177,20±34,92). The area of damage on 1 cm2reached 13,10±1,92 mm2total area - 785,70±151,42 mm2. In the colon area of the ulcer surface occupied 64,70±of 9.55 mm2.

Example 2. Five-day introduction to 4.5 mgkg indometacin in all animals caused ulceration in the stomach with signs of atrophy of the mucosa. In 62.5 cases there were signs of intestinal bleeding. The size of ulcers was between 0.1×0.1 to 5.0×7,0 mm Total area ulcers at 71.6 per cent was presented to deep ulcers. The total number of ulcers was 16.0±1,47, the number of deep ulcers - 7,13±1,60, surface - 8,88±0,93. The area of the ulcer surface 1 animal was 22,7±6,28 mm2the area of deep ulcers - 16,26±5.4 mm2, surface - to 6.43±1,86 mm2(table 2).

The ulceration in the small intestine occurred within 30-60 cm distal. Ulcer defects had dimensions 1,0×1,0-3,0×4.5 mm, the number of ulcers on 1 cm2from 1 to 9. In 62.5% of cases ulcers were performable the intestinal wall. All animals were observed thinning of the intestinal wall. Four animals with perforation of the intestinal wall into the abdominal cavity was found 0.5 to 2.0 ml of turbid fluid is yellow. One rat was evidence of the ulcer penetration into the tissue of the liver. In the colon was observed multiple defects drain of character.

The number of ulcers in the small intestine was 156,1±50,59 1 animal, area ulcers - 996,3±200,0 mm2. In the colon area of the ulcer was achieved 69,73±22,58 mm2.

Thus, the carried out researches have revealed a pronounced ulcerogenic effect of exchange rate call is placed indometacin on the mucous membrane of the stomach and intestines outbred rats. This model of ulcer formation takes into account the pathogenetic mechanisms of the gastrointestinal tract in exchange oral nonsteroidal anti-inflammatory drugs, allows us to strictly control the amount of input dose and can be used to study methods of prevention and treatment of gastro - and enteropathy induced by the use of nonsteroidal anti-inflammatory drugs.

superficial ulcers
Effect of 5-day injection of indomethacin at a dose of 5 mg/kg intragastrically to ulceration in the stomach, the small and the large intestine nonlinear white rats.

Table 1
StomachSmall intestineColon
The number of animalswith ulcers100%100%100%
with bleeding50%--
perforated ulcers-60%-
The number of ulcers (1 animal)the total number of12,0±0,79177,2±34,92-
deep ulcers9,60±0,67--
2,40±0,60--
The area of the ulcer surface mm2(1 animal)the total areaone-21.32±3,83785,70±151,4264,70±of 9.55
deep ulcers19,38±3,72--
superficial ulcers1,94±0,47--

Effect of 5-day injection of indomethacin at a dose of 4.5 mg/kg intragastrically to ulceration in the stomach, small and large intestines white nonlinear rats

Table 2
StomachSmall intestineColon
The number of animalswith ulcers100%100%100%
with bleeding62,5%--
perforated ulcers-62,5%-
The number of ulcers (1 animal)the total number of16,0±1,47156,1±50,59-
deep ulcers7,13±1,60 -
superficial ulcers8,88±0,93--
The area of the ulcer surface mm2(1 animal)the total area22,70±6,28996,30±200,069,73±22,58
deep ulcers16,26±5,41--
superficial ulcersto 6.43±1,86--

The simulation method ulcerative lesions of the stomach and intestines through the introduction of a drug, characterized in that the animals injected with indomethacin at a dose of 4.5-5 mg/kg rats intragastrically after two hours without food and water daily for 5 days.



 

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