动物造模,兔肝硬化 zi-bio 2024-02-18 696

　　1. Animal modeling materials: Healthy 3-month-old New Zealand white rabbits, weighing (1.8 ± 0.2) kg; Medications: Full price nutritional pellet rabbit feed, CCl4, olive oil, edible ethanol.

　　2. Modeling method: The experimental group and the control group were fed with normal rabbit feed every day. The experimental group was given a subcutaneous alternating injection of 500mL/L CCl4 olive oil solution twice a week at a rate of 1.5ml/kg on the outer side of both lower limbs; Starting from the third injection, the dosage was changed to 2.5ml/kg for 2 weeks; Starting from the 5th week, it will be further reduced to 1.5ml/kg, twice a week; Starting from the first week, 10ml of 300ml/L edible ethanol should be administered daily. The control group was only injected with the same volume of olive oil and drank water normally; Save blood on weekends 0, 2, 4, and 8 to evaluate liver function indicators.

　　3. Modeling principle: CCl4 is activated by liver microsomal cytochrome P450 to generate CCl3, which attacks the phospholipids on the liver cell membrane and causes lipid peroxidation to damage the membrane structure; CCl4 also forms covalent bonds with proteins, damaging mitochondria and affecting the tricarboxylic acid cycle, leading to suffocation and death of liver cells. Repeated use of low concentration CCl4 can cause liver damage, repair, damage, and ultimately lead to cirrhosis.

　　4. Changes after modeling: During the modeling process, experimental animals experience reduced activity, mental lethargy, lack of appetite, slow response to external stimuli, fluffy and dull fur, significant weight loss in the early stages, slow weight gain in the later stages, and most of them have loose stools. When touched by hand, the muscle layer on both sides of the spine disappears, and the bone sensation is obvious; The normal group of rabbits has shiny hair, lively posture, normal appetite and bowel movements, no drowsiness, and abundant muscle layers on both sides of the spine.

　　The normal liver texture is soft and smooth, with a uniform dark red color and a size within the normal range. At the end of the 8th week, the experimental group of rabbits showed a reduction in liver volume, with small nodules or granules on the surface, no elasticity, and a hard texture. The normal liver has a complete structure of liver lobules, neatly arranged liver cell cords, clear portal areas, and a radial distribution of liver sinusoids. In the second week of the experiment, liver congestion, edema, and enlargement were observed. Liver cells near the central vein of the liver lobules were swollen and nearly circular, with narrowing of the hepatic sinusoids and worsening of inflammatory reactions. In the fourth week of the experiment, the liver color was dim and the swelling was slightly reduced. Liver cells around the central vein were necrotic in dots and patches, with some lobular structures collapsing and a small amount of fibrous connective tissue proliferation; On the weekend of 6, diffuse fibrous tissue proliferation was observed in the liver, with disordered liver lobular structure and the formation of atypical pseudolobules. During the 8-9 weeks of the experiment, the necrosis was more extensive and severe, with collagen fibers radiating from the central vein and portal area interweaving into a network and extensive formation of hepatic pseudolobules. The cytoplasm of liver cells in the pseudolobules was extremely loose, with severe lipid changes and large vacuoles.

　　Before the liver function test, the average ALT level was 883.5nkat/L, which increased to 5451.1nkat/L after 2 weeks of modeling, and then gradually decreased: 0-8 weeks: γ- Glutamyltransferase（ γ- Glutamyltransferase (GGT), alkaline phosphatase (AKP), and A/G values all gradually decrease; The AST value also showed a transient increase.