动物造模,药效评价,膀胱癌 z-bio 2024-07-08 384

　　[Modeling mechanism] There are two types of ideal chemical carcinogens to induce animal bladder cancer: nitroso compounds represented by N-butyl-N - (4-hydroxybutyl-1) - nitrosamine (BBN) and N * methyl-N-nitrosourea (MNU) and nitro compounds represented by N - [4- (5-nitro-2-furyl) -2-thiazolyl] formamide (FANFF) Furans. The lesions of bladder cancer are usually multiple. bladder cancer induced by FANFT begins to infiltrate into the basement membrane and gradually infiltrates into various tissues, from mild hyperplasia to invasive cancer, and finally develops into distant metastasis. Under electron microscopy, the cancer cells are irregularly arranged, with varying sizes and shapes, appearing circular, irregular, and spindle shaped. The nucleus is large, often with increased chromatin and edges, and the nucleolus is large and often close to the nuclear membrane.

　　【 Modeling Method 】

　　1. Select about 250g F344 male rats, and feed the weaned rats with 0.2% dose of FANFT feed, which can cause bladder cancer. If such rats take FANFF for a lifetime or take it for 25-36 weeks, and randomly control the diet, all rats will die of bladder cancer before the age of 20 months.

　　2. The further metabolite of BBN, N-butyl-N - (3-carboxypropyl) nitrosamine, was excreted from the urine of nude mice model of bladder cancer in situ, and contacted with the urothelium to cause canceration. The gastric lavage method has a high tumor induction rate with small doses and multiple administration. The animal model of bladder cancer can also be induced by intraperitoneal injection. The rate of inducing cancer is almost the same as that of gavage, but acute poisoning and adhesive intestinal obstruction are prone to occur in animals. FANFF is generally mixed with food to feed animals, with a commonly used concentration of 0.02%. MNU is a direct carcinogen that requires bladder irrigation, which poses a risk of animal urethral injury, secondary urinary tract infections, and bladder stones.

　　【 Model characteristics 】 Within 2 weeks of taking FANFT, all rats showed proliferative damage to their bladder. After 8 weeks of taking FANFT, with an increase in proliferative damage, nodular and papillary damage appeared, especially nodular damage gradually expanding into the bladder cavity. If the survival time of the rats was long enough, they could penetrate the muscle layer and infiltrate the surrounding tissues.

　　The carcinogenic effect of bladder cancer can be divided into two stages. FANFT can be used as an initial carcinogen. This model is helpful for studying possible early and late carcinogens.

　　[Evaluation and application of models] bladder cancer is one of the most common malignant tumors of the urinary system. Inducing bladder tumors in animals is an effective way to study the etiology, pathology, prevention and treatment of human bladder cancer. The occurrence of bladder cancer in rats experienced three important morphologic stages similar to human primary cancer: epithelial hyperplasia stage, papilloma formation stage and canceration stage. The carcinogenic dose and action time were positively correlated with the canceration cycle.