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INVENTION
Patent of the Russian Federation RU2269161

METHOD OF MODELING OF LIVER-DAMAGE TO THE GASTRIC AND THE INTELLIGENT

The name of the inventor: Zorkina Angelina Vladimirovna (RU); Inchina Vera Ivanovna (RU); Yamashkina Ekaterina Ivanovna
The name of the patent holder: State institution of higher professional education "Mordovian State University named after NP Ogarev"
Address for correspondence: 430000, Saransk, ul. Bolshevistskaya, 68, Moscow State University named after NP Ogarev, Department of Patents and Standards
Date of commencement of the patent: 2004.04.08

The invention relates to the field of experimental medicine, in particular to gastroenterology, and concerns the modeling of ulcerative lesions of the stomach and intestines. For this, indomethacin in a dose of 4.5-5 mg / kg of body weight is administered intragastrically to experimental rats after two hours without food and water. The introduction is continued for 5 days. The method ensures the achievement of ulceration, accompanied by bleeding and perforation of ulcers, simultaneously in the stomach, in the small and large intestine.

DESCRIPTION OF THE INVENTION

The invention relates to the field of medicine, namely, to the creation of a method for modeling ulcerative lesions of the gastrointestinal tract, and can be used to experimentally study the processes of ulcer formation in the mucous membrane of the stomach and intestines, induced by the intake of nonsteroidal anti-inflammatory drugs, and to search for new means of prevention and treatment Ulcerogenesis.

It is known to simulate ulcerative lesions of the stomach by intraperitoneal administration of indomethacin in rats at a dose of 25-30 mg / kg once (LN Sernov, VV Gatsura "Elements of Experimental Pharmacology." - M., 2000, p.219).

However, this model does not fully reflect the pathophysiological mechanisms of the damaging effect of non-steroidal anti-inflammatory agents on the mucous membrane during long-term admission and is based on acute single intoxication leading to the death of a part of the experimental animals.

The technical result consists in the creation of the most physiological model of ulcerative lesions of the gastrointestinal tract, which is as close as possible to that of individuals taking long-term non-steroidal anti-inflammatory drugs.

The essence of the invention lies in the fact that the method for modeling ulcerative lesions of the stomach and intestines is carried out by administering indomethacin in animals at a dose of 4.5-5 mg / kg intragastrically after two hours of food and water-free daily for 5 days.

The method is carried out as follows. Indigenous white rats of both sexes weighing 180-210 grams are taken. Indomethacin is administered to rats 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, animals were slaughtered by decapitation. At autopsy, the picture of the mucous membrane of the stomach and intestines was evaluated: the number and area of ​​ulcerative defects, the presence of signs of gastric bleeding, intestinal wall perforation, the ratio of deep and superficial ulcerative lesions.

Example 1 . Course introduction of indomethacin in a dose of 5 mg / kg had ulcerogenic effect on the gastric mucosa in 100% of cases. Half of the animals showed signs of intragastric hemorrhage. The membrane part of the stomach sharply thinned, the mucous membrane of the muscular part became loose. Ulcerative defects were localized in both parts, their sizes varied from 0.1 × 0.1 to 4 × 9 mm. At the same time, 78.9% of all ulcers were presented with deep ulcers, and their area was 92.0% of the total area of ​​the ulcerous surface (Table 1).

The total number of ulcerative defects 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 lesion against the background of indomethacin injection reached 21.32 ± 3.83 mm ² , the area of ​​deep defects was 19.38 ± 3.72 mm ² , the surface area was 1.94 ± 0.47 mm ² per animal.

Against the background of the introduction of 5 mg / kg of indomethacin by the probe method in the intestinal mucosa, ulcerative defects of various depths were formed in all animals. Primarily, ulceration occurred in the distal part of the small intestine for 45-55 cm and in the large intestine. In the small intestine, ulcers measured from 1 × 1 to 3 × 5 mm, the number of ulcers from 2 to 8 per 1 cm ² . In 60% of animals, ulcers perforated the intestinal wall. The small intestine was stretched, the wall was thinned to transparency. Three animals showed signs of diffuse peritonitis in the autopsy: 3-3.5 ml of a turbid yellowish-hemorrhagic fluid were found in the abdominal cavity. The rest of the stomach and loops of the intestine stood out badly. In the large intestine, multiple defects were observed up to the muscle layer. Often they wore a draining character, in some places a continuous layer covered the inner surface of the intestine.

The number of ulcerative defects in the small intestine per animal was 3.80 ± 0.64 per cm2 (total 177.20 ± 34.92). The lesion area per 1 cm ² reached 13.10 ± 1.92 mm ² , the total area - 785.70 ± 151.42 mm ² . In the large intestine, the area of ​​the ulcer surface occupied 64.70 ± 9.55 mm ² .

Example 2 . A five-day administration of 4.5 mg / kg of indomethacin in all animals caused ulceration in the stomach with signs of mucosal atrophy. In 62.5 cases, signs of intragastric hemorrhage were noted. The sizes of ulcer defects were from 0.1 × 0.1 to 5.0 × 7.0 mm. The total area of ​​ulcerative defects was 71.6% represented by 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 ulcerous surface per animal was 22.7 ± 6.28 mm ² , the area of ​​deep ulcers was 16.26 ± 5.4 mm ² , and the surface area was 6.43 ± 1.86 mm ² (Table 2).

Ulceration in the small intestine occurred over 30-60 cm of the distal part. The ulcer defects were 1.0 × 1.0-3.0 × 4.5 mm, the number of ulcers per 1 cm ² was from 1 to 9. In 62.5% of the cases, the ulcers perforated the intestinal wall. All animals showed thinning of the intestinal wall. In four animals with a perforation of the intestinal wall in the abdominal cavity, 0.5-2.0 ml of a turbid liquid of yellow color was detected. One rat noted signs of penetration of the ulcer into the liver tissue. In the large intestine, multiple defects of a draining character were observed.

The number of ulcerative defects in the small intestine was 156.1 ± 50.59 per animal, and the area of ​​ulcers was 996.3 ± 200.0 mm ² . In the large intestine, the area of ​​ulcers reached 69.73 ± 22.58 mm ² .

Thus, the performed studies revealed a pronounced ulcerogenic effect of the course introduction of indomethacin on the mucous membrane of the stomach and intestine of white non-native rats. This model of ulceration takes into account the pathogenetic mechanisms of the lesion of the gastrointestinal tract with oral oral intake of non-steroidal anti-inflammatory drugs, allows to accurately control the amount of the administered dose and can be used to study the methods of prevention and treatment of gastro- and enteropathies induced by the intake of non-steroidal anti-inflammatory drugs.

CLAIM

A method for modeling ulcerative lesions of the stomach and intestines by administering a medicament, characterized in that animals are administered indomethacin at a dose of 4.5-5 mg / kg rat mass intragastrically after two hours of food and water-free daily for 5 days.

print version
Date of publication 29.03.2007gg

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