疾病动物模型,营养性脂肪肝模型 z-bio 2021-03-10 349

　　[Modeling method] Methionine-choline deficiency (MCD) diet is often used to induce classic NAFLD animal models. The MCD diet is rich in carbohydrates (40%) and fat (10%), but lacks methionine and choline, which are involved in the β-oxidation of fatty acids in liver cells and the synthesis of low-density lipoproteins. Feed rodents such as rats and mice. High-fat diet (HFD) model: Use HFD to feed rats, guinea pigs, rabbits, dogs, etc. (carbohydrates, fats and proteins account for 52%, 30% and 18% of total calories, respectively). can do. Induce NAFLD.

　　Complete parenteral nutrition (TPN) model: deep veins (such as superior vena cava) can be intubated in adult rats. Connect the infusion pump to continuously inject non-protein nutrients (such as high glucose and amino acid high nutrients or glucose and fat emulsion). Tsukamato-French rat model: In 1984, Tsukamato-French et al. surgically transplanted a gastric tube into a rat, and continued to inject ethanol-containing liquid food to increase the rat’s ethanol concentration to 200-300 mg/ dl. I kept it. blood. We created three models, which lasted for several months or fixed them in calories at the same time, and continued to provide liquid food with a small amount of corn oil (4.9% calories) from the stomach tube for 30 days.

　　Ethanol gavage model: In the process of daily solid diet and ethanol (11-12 g/kg) rat gavage for 4 weeks, it may cause liver histological damage like the Tsukamoto-French method. Use high-concentration solution (about 60°) (5 ml/100 g) and malnourished feed (wheat flour, secondary flour, grass meal, soybean meal, 2:1:1 formula) to take orally once a day. ). 1:1 ratio, and a small amount of soybean oil and salt), orally on an empty stomach, fasting every night until the next morning, can produce alcoholic fatty liver for 75 consecutive days. The mixture of wine, corn oil and pyrazole can also be used for forced feeding (wine 8-12 g/kg, corn 2 g/kg, pyrazole 24 mg/kg), and the molding cycle is 12 weeks.

　　[Model Features]

　　MCD model: simple and easy to implement, but the disease and its severity are related to the sex, strain and type of the mouse. After feeding the mice for 1-2 weeks, there was obvious fatty liver, and the liver developed after 2 weeks. With necrotizing inflammation followed by perinasal and central venous fibrosis, serum transaminase was significantly increased, and liver lipid oxidase gene expression was up-regulated; Sprague Dawley rats’ diet progressed slowly and appeared within two weeks of modeling liver and fatty liver Fat and transaminase increased slightly, oxidative stress occurred at the 5th week, liver inflammation and necrosis, and liver fibrosis at the 12th week. Mice fed the MCD diet lose weight, so their muscle and body fat content are reduced, and may develop hypoglycemia in insulin-sensitive peripheral tissues after 4 weeks of modeling.

　　HFD model: Sporadic hepatic steatosis appeared in the 4-week model, simple fatty liver appeared at 8 weeks, steatohepatitis appeared at 12 weeks, liver inflammation and necrosis worsened at 16 weeks, and fibrosis around the sinusoid The disease and inflammation of fat worsened in 2000. After 24 weeks, the degree of fibrosis was slightly reduced and worsened, and even intermittent fibrosis appeared. Rat abdominal visceral fat increased, peripheral blood free fatty acids and total cholesterol gradually increased, portal toxemia, liver cell mitochondrial damage, oxidative stress, lipid peroxidation damage, liver Kupffer cell activation accompanied. I have insulin resistance. However, the increase in body weight and blood TG is unclear.

　　TPN model: If the non-protein energy in the nutrient solution accounts for more than 33% of the total calories or the total intake accounts for more than 83% of the total calories, the rat liver will have obvious steatosis. When a high-nutrient solution containing high glucose and amino acids is used, the non-protein energy required increases to 146% [equivalent to 350 non-protein calories (kg? D)], while the nitrogen needs to increase 335% [equivalent to? 2.7] g amino acid nitrogen/(kg·D)], liver hypertrophy will appear in half a day, and liver glycogen and fat will increase within two days. By day 4, liver fat had increased fourfold, and liver essential fatty acid deficiency gradually worsened.

　　Ethanol oral administration model: The animal's body weight gradually increases and the food intake is significantly reduced. Most animals have sparse stools. Histopathology showed hepatocyte edema and balloon-like changes, the widespread appearance of round lipid droplets of various sizes in the cytoplasm, and the formation of regular or irregular eosinophils or ethanolic vitreous. The inflammatory cells in the portal vein were clearly infiltrated, showing the proliferation of collagen fibers and the swelling of sinusoidal endothelial cells.