动物造模,药效评价,诱发性肝癌 z-bio 2024-08-02 600

　　The induced liver cancer animal model refers to the use of chemical, physical, and biological carcinogenic factors on experimental animals to simulate the cyclic changes of liver injury fibrosis malignant transformation and induce the formation of liver cancer in animals. At present, chemical carcinogens are the main inducers of liver cancer, and commonly used substances that cause liver cancer include diethylnitrosamine (DEN), dimethylaminoazobenzene (DBA), 2-acetylamino acid (2-AAF), o-aminoazotoluene (OAT), and aflatoxin (AF).

　　[Method of Modeling]

　　DEN induction model: When used alone, Sprague Dawley rats or Wistar rats can be given 0.25% DEN aqueous solution by gavage at a dose of 10mg/kg once a week, and 0.025% DEN aqueous solution can be supplied to the animals for drinking daily for 6 months. Alternatively, a one-time intraperitoneal injection of a sterile aqueous solution of 0.5% DEN (100mg/kg) can be administered, and 100mg/L of DEN sterile aqueous solution can be continuously supplied for free drinking until 16 weeks after 1 week; During the 9th to 11th week, sterile water was supplied instead. DEN can also be combined with 2-AAF, also known as Solt Farber cancer induction method: rats are given a one-time intraperitoneal injection of 200mg/kg DEN solution. After 2 weeks, they are fed a diet containing 0.02% 2-AAF for 14 days. In the third week, most of the liver is removed, and in the fourth week, they are fed a normal diet.

　　DBA induction model: fed with diet containing 0.06% DAB and controlled for vitamin B2 content (≤ 1.5-2.0mg/kg), continuously fed for 4-6 months.

　　2-AAF induction model: Sprague Dawley rats were fed with 0.05% 2-AAF feed. For 3 to 4 consecutive months.

　　OAT induction model: Apply 1% OAT solution (10mg/ml) to the skin between the two shoulder blades of mice, once every other day, 2-3 drops each time, for 7-8 weeks.

　　AF induction model: Rats with liver cancer were fed with a monthly feed containing 0.001-0.015ppm for 6 months. Alternatively, dissolve AF in dimethyl sulfoxide (DMSO) and inject it intraperitoneally once a day at a dose of 400 μ g/kg for 2 consecutive weeks before stopping the injection. Inject AF at a dose of 0.75-1.50 mg/kg at once, and perform liver resection after 2 weeks.

　　【 Model Features 】 DEN is the most common chemical carcinogen, with a carcinogenic rate of 80% in rats. The DBA method can cause liver cancer within 6 months, with a cancer induction rate of 60%. Pre cancerous lesions can appear after 3 weeks of 2-AAF induction. Under the microscope, liver cells appear as oval shaped cells with varying sizes of cancer nests and nodules. After 3-4 months, 80% to 90% of animals develop liver tumors. Nodules appeared 8 weeks after administration using the OAT smear method, and liver cancer was induced in mice 7 months later, with a cancer induction rate of about 50%. The incidence of liver cancer induced by AF in rats is 80%, but the disease course is long and the tumors are mostly diffuse nodular.

　　Model evaluation and application: Induced models have insidious onset and long induction cycles. The mortality rate of animals during the induction process is relatively high, and there are also significant individual differences in the location, number, and timing of liver cancer occurrence. At present, this model is mostly used for research on the etiology, genetics, and biology of liver cancer.