动物造模,药效评价,脂肪肝 z-bio 2024-09-02 386

　　(1) The replication method involves administering 0.15% carbon tetrachloride (CCk) 10mg/kg body weight to mice at once, or intraperitoneal injection of D-galactosamine (D-Gal) 800mg/kg body weight; Alternatively, rats can be subcutaneously injected with a 40% CCl4 solution at a dose of 4-5ml/kg body weight, followed by another injection of 2ml/kg body weight via the same route after 3 days. Alternatively, tetracyclines such as tetracycline, chlorotetracycline, and demethylamycin can be intraperitoneally injected at a dose of 0.25mmol/kg body weight. Alternatively, rats can be fed a diet containing 0.25% ethionine for 2 consecutive weeks. After administering or injecting the chemical substance for a certain period of time, whole blood will be drawn and the liver will be removed for biochemical and histological examination.

　　(2) Model characteristics: After a single dose of CCl4 or intraperitoneal injection of D-Gal in mice, serum ALT and AST levels increased 24-48 hours later, and liver cells became turbid and vacuolated, showing severe eosinophilic and fatty changes. High levels of ALT and AST persisted until 96 or 72 hours, respectively. Subcutaneous injection of CCl4 in rats resulted in moderate to severe hepatic steatosis with inflammation and necrosis one week later; Intraperitoneal injection of tetracycline like substances resulted in significant vesicular steatosis in liver cells several hours later, reaching its peak at 24 hours; Adding ethionine to the diet resulted in moderate to severe hepatic steatosis and fibrosis after 2 weeks.

　　(3) In clinical comparative medicine, improper use of drugs or toxins is also one of the causes of fatty liver. Common chemicals that can cause fatty liver include CCl4, chloroform, galactosamine, actinomycin, growth hormone, adrenal cortex hormone, tetracycline, and some lipid-lowering drugs. When using chemical substances to replicate animal models of fatty liver, special attention should be paid to the selection of animal species, age, and gender. Mice are highly sensitive to CCl4, while rats have a certain tolerance. Using CCl4 as an inducer to replicate similar mouse and rat models, the latter requires a dose 50-100 times higher than the former, and adult or male rats are more sensitive to CCl4 than underage or female rats. In terms of model mechanism, CCl4 causes liver cell damage and steatosis in model animals through the free radical lipid peroxidation pathway. Tetracyclines interfere with lipoprotein synthesis by inhibiting mitochondrial oxidative phosphorylation, thereby hindering the excretion of triglycerides from the liver. In terms of organizational morphology, CCl4 model liver cells can exhibit large vesicular steatosis, while tetracycline and ethionine exhibit small vesicular steatosis. The biggest advantage of using chemical substances to induce experimental fatty liver models is its simplicity and speed. However, the animal mortality rate is relatively high, and there are significant differences in the main causes and pathogenesis compared to non-alcoholic fatty liver in humans. Therefore, attention should be paid to its application.