动物模式,脂肪肝 z-bo 2020-08-07 586

　　(1) Replication method PEPCK-nSREBP-la mice, artificially cultured transgenic mice that develop transient fatty liver after birth, can regenerate fatty liver after weaning with a low-sugar and high-protein diet. The aP2-nSREBP-1c mice belong to artificially cultured transgenic animal models. Ob/ob mice, fa/fa rats, and JVS mice are natural mutant animal models. FLS mice, a fatty liver animal model cultivated by inbred mating method.

　　(2) Model characteristics: The transcription factors of nSREBP-1c in aP2-nSREBP-1c mice accumulate in the nuclei of white and brown adipocytes. These adipocytes cannot be completely differentiated. The weight of white adipose tissue (WAT) increases significantly, and the liver It is full of triacylglycerol and manifests as hyperinsulinemia, insulin resistance and fatty liver. Ob/ob mice or fa/fa rats show overfeeding, obesity, hyperinsulinemia, hyperglycemia (insulin resistance) and hyperlipidemia, and develop fatty liver. The weight of JVS mice (juvenile visceral steatosis mouse, JVS) increases rapidly at 4 to 5 weeks after birth, showing mild to moderate fatty degeneration of liver cells. When FLS mice were born, the liver lobules contained quite a lot of small lipid droplets. Large lipid droplets appeared with age. The content of liver triacylglycerol increased significantly, and the activity of aspartate aminotransferase and alanine aminotransferase increased.

　　(3) Comparative Medicine The uptake, synthesis, oxidation and transport of lipids by liver cells are mainly regulated by enzymes in liver cells. Natural mutations of animal-related genes or artificial changes in their genetic factors can induce liver steatosis in experimental animals. PEPCK-nSREBP-1a mice and aP2-nSREBP-1c mice belong to animal models that promote liver adipogenesis gene overexpression. SREBP-1 is a transcription factor that can activate the transcription of many genes involved in fatty acid and cholesterol biosynthesis. Hepatocytes specifically overexpressing nSREBP-1a in transgenic mice can activate phosphoenolpyruvate carboxykinase (PEPCK) enhancers by feeding carbohydrates and high protein diets, driving liver expression from cholesterol regulators Protein-1a (sterol regulatory etement binding protein-1a, SREBP-1a) is a mainly positively charged protein fragment that induces the mRNA of a variety of lipogenic enzymes to form fatty liver. The aP2-nSEBP-1c mice have certain characteristics of PEPEC-nSREBP-1a mice. Given the treatment of Xenin, it can cure his insulinemia, insulin resistance and fatty liver. Ob/ob mice and fa/fa rats are natural mutation models that promote liver fat production. Ob/ob mice prevent the synthesis of leptin due to natural mutations, leading to increased liver fatty acid input, fatty acid synthase and liver cell uncoupling protein (UCP)-2mRNA and protein expression. But the fatty acid cannot get ATP in the metabolism of mitochondria. The Fa (fatty) mutation in fa/fa rats is a point mutation near codon 269 of the ligand binding region of the leptin receptor, which affects the receptor's intracellular activation and/or signal transmission. Fak mutation is a point mutation that causes codon 763 in front of the transmembrane region to stop premature. Unlike the Fa mutation, the Fak mutation prevents the leptin receptor from inserting into the cell membrane. Regardless of the mutation, the pure sheds are manifested as overeating, obesity, insulin resistance diabetes and hyperlipidemia. JVS mice belong to an animal model that reduces liver fat clearance genes. Due to the primary carnitine deficiency in JVS mice, the process of fatty acid transport to human mitochondria is blocked, fatty acid beta oxidation is impaired, and fatty acids accumulate in the liver. FLS mice belong to a multi-gene model. FLS mice can develop fatty liver spontaneously without obesity or diabetes. This fatty liver model has nothing to do with alcohol and obesity. The genetic analysis is the result of polygenic effects. It is a very promising fatty liver animal model.