疾病动物模型,自发性脂肪肝动物模型 z-bio 2021-12-15 324

　　[Modeling mechanism] Due to the mutation of the key gene of fat metabolism in liver cells, the fat metabolism disorder is caused, which leads to the imbalance of liver fat input and output.

　　【Features of the model】ob/ob mice (ob/ob mice) are mice with recessive genetic mutations accidentally discovered by the Jackson Laboratory of the United States in 1949. They are currently the most commonly used NAFLD model abroad. Ob/ob mice are due to spontaneous mutations in the ob gene encoding the appetite-suppressing hormone leptin, unable to synthesize leptin, leading to overeating, obesity, hyperinsulinemia, hyperlipidemia, and obvious hyperglycemia. Histopathological changes include fatty degeneration of liver cells. Normal feed feeding only occurs with simple fatty liver, and will not evolve into nonalcoholic steatohepatitis (NASH), unless a diet lacking methionine and choline or a high-fat diet or coexisting other liver injury factors.

　　db/db mice or fa/fa (Zucker) rats are caused by mutations in the db gene (or fa gene) of the leptin receptor, which leads to leptin resistance, resulting in a phenotype similar to ob/ob mice .

　　FLS mouse (fatty liver shionogi mouse) is a new strain of mice with fatty liver without overeating, obesity and diabetes, which was reported in 1999 by Soga et al. through inbreeding. Small fat particles accumulate in the whole liver lobules of neonatal FLS mice, and they gradually increase with age. The content of triglyceride (TG) in the liver is 5 times higher than that of dd Shionogi (DS) mice of the same age, but There is no abnormality in blood lipids. Monocyte infiltration and clusters of foam cells appeared in the liver of FLS mice from 2 to 4 months, accompanied by elevated serum transaminase levels. The number of large lipid droplets in the liver cells of FLS mice at 4-6 months of age is less than before, and FLS mice at 12 months are prone to develop spontaneous hepatocellular adenoma (HCA) or hepatocellular carcinoma (HCC).