Modification of a model of non-alcoholic fat liver disease in rats with a сombination of a hypercaloric diet and hypodynamia

A V Bunjat,S V Okovityi,V E Karev,D Ju Ivkin,A V Karavaeva,O M Spasenkova,A N Kulikov,N V Kirillova

doi:10.33380/2305-2066-2021-10-4(1)-155-165

Abstract

Introduction. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, and non-alcoholic steatohepatitis is the second most common cause of liver transplantation in the adult population. An urgent task is to find and develop an optimal model of NAFLD in laboratory animals, which would reproduce all the features of this disease in the clinic.Aim. Modification of the NAFLD model in laboratory animals (rats), which allows the obtained data to be transmitted to humans as fully as possible.Materials and methods. The study was conducted on 52 outbred white male rats of the same age. As the basis of the model, a hypercaloric high-fat diet was used with the addition of food appeal enhancers (sodium glutamate and liquid shrimp extract) and for the first-time conditions of hypodynamia were used – restriction of the motor activity of animals using specially designed cells, in which an individual 11 × 18 cm cell was allocated for each individual. The duration of the study was 12 months. In the course of the experiment, body weight, physical performance, biochemical parameters of blood serum and urine in dynamics were assessed, and lethality was recorded. After the end of the study, the mass of internal organs, visceral and epididymal fat was analyzed, and a histological examination of the liver was performed.Results and discussion. In the course of the experimental study, the development of NAFLD in rats of the control group of animals was histologically confirmed. A high mortality rate was revealed in the group of animals with pathology. Compared with animals of the intact group, a statistically significant increase in their body weight, liver weight, visceral and epididymal fat, a decrease in physical performance, disturbances in lipid, carbohydrate and protein metabolism were revealed, as well as signs of deterioration of the protein synthesis and excretory functions of the liver.Conclusion. A number of advantages of the NAFLD model with a combination of a hypercaloric diet and hypodynamic conditions were revealed, including the similarity of the conditions for the formation and pathogenesis of the disease in experimental animals and humans, which ensures the adequacy of data translation from preclinical practice to clinical practice.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, and non-alcoholic steatohepatitis is the second most common cause of liver transplantation in the adult population
Modification of the NAFLD model in laboratory animals, which allows the obtained data to be transmitted to humans as fully as possible
As the basis of the model, a hypercaloric high-fat diet was used with the addition of food appeal enhancers and for the first-time conditions of hypodynamia were used – restriction of the motor activity of animals using specially designed cells, in which an individual 11 × 18 cm cell was allocated for each individual

Summary

МАТЕРИАЛЫ И МЕТОДЫ

Все исследования проводились согласно требованиям решения совета Евразийского экономического союза в Сфере обращения лекарственных средств от 03.11.2016 No 81, с одобрения биоэтической комиссии ФГБОУ ВО СПХФУ Минздрава России, протокол БЭК NAFLD-Rats-2020 от 18.01.2020 г. В ходе исследования было выявлено, что все заявленные вещества значимо повышают суточное потребление корма животными по сравнению с контрольной группой, однако наибольшее потребление из всех наблюдали в группе с экстрактом креветки (в 1,9 раза по сравнению с группой на стандартном корме), поэтому он, вместе с глутаматом натрия, был выбран для дальнейших исследований в качестве аттрактанта. Что наряду с гиперкалорийным питанием, гиподинамия является одним из важнейших факторов риска развития НАЖБП, в использованную модель было введено ограничение двигательной активности животных с помощью специально разработанных клеток, в которых для каждой крысы выделялась индивидуальная ячейка размерами 11 × 18 см. В контрольных точках эксперимента (180-й и 360-й дни исследования) оценивали физическую работоспособность с помощью тредмила (Treadmill System for rats, TSE, Германия) после предварительного обучения. Критерием статистической достоверности получаемых выводов мы считали общепринятую в медицине величину р < 0,05

РЕЗУЛЬТАТЫ И ОБСУЖДЕНИЕ

Findings

Контроль Control