动物模型 z-bo 2022-02-02 463

　　[Modeling mechanism] Methylnitrosonitroguanidine (N-methyl-N'-nitrosonitroguanidine, MNNG) and methylcholestene (MC) are usually used. MNNG is a polycyclic hydrocarbon, which has a strong carcinogenic effect and can cause the production of nitric oxide in the tissues, thereby aggravating the malignant transformation of cells. MC is a powerful direct carcinogen, which does not depend on enzyme metabolism, but directly acts on the gastrointestinal mucosa. In particular, oral administration is highly carcinogenic to the stomach.

　　[Modeling method]

　　1. MNNG-induced gastric adenocarcinoma in rats was selected from 100 g Wistar male rats and free drinking water, 0.01% MNNG (100 μg/ml) was added every other day, and no other drinking water was given during the experiment. In addition, the use of methyl nitrosoacetate can add 2 mg/kg body weight to the drinking water of BD rats and drink it 5 times a week. After 520 days, all rats developed gastric adenocarcinoma.

　　2. MNNG-induced mouse gastric adenocarcinoma was selected from Kunming mice weighing 18-22 g, and then 500μg/ml MNNG solution was administered to the mice at a dose of 0.4 ml/dose three times a week for 12 months Then increase to 0.6 ml.

　　3. MC-induced rat gastric adenocarcinoma was selected from Wistar rats weighing 120-200 g. After aseptic surgery, a knot containing MC is placed in the mucosa of the proventriculus. One end of the knot containing the MC is tied with an ordinary thin thread. Put a bunch of knots into a small glass test tube containing MC, and gently heat with an ethanol lamp to liquefy MC and make it penetrate into the knots. The MC concentration is 50-100 mg, and each line binds approximately 5 mg MC. Open the abdominal cavity under aseptic conditions and make a 2-3 mm incision in the anterior wall of the anterior abdominal wall. The suture needle enters the gastric cavity through the incision and passes through the mucosa from the smaller curvature of the pylorus to the muscle layer and serosa. The nodules are fixed half a day after the operation and are semi-fixed.

　　Four. MC-induced gastric cancer in mice was aseptically administered about 20 g of mice, and a knot containing MC was tied on the gastric mucosa of the gland. The MC knot is made of ordinary thin wire with a knot at one end. Put the knot into a small glass test tube containing MC and gently heat it with an ethanol lamp to liquefy the MC and form a knot. The MC concentration is 0.05 to 0.1 g of 20 to 10 lines of 20-methyl cholesterol. Four to eight months after surgical embedding can induce successful stomach cancer. Using 0.25 ml/kg body weight of asymmetric nitrosamines, all animals developed anterior gastric cancer papillary cancer after 3 months, and 85%-100% of anterior gastric cancer papillary cancer after 7-8 months. Kunming is the most sensitive, followed by strain A, and 615 is the least sensitive. [Characteristics of the model] The incidence of gastric cancer in rats induced by MNNG is about 80%. It is mainly well-differentiated adenocarcinoma that has metastasized to the lymph nodes of the liver and shoulder. The induction rate of MNNG-induced gastric adenocarcinoma in mice is 23%, which is a well-differentiated adenocarcinoma that can induce predifferentiated gastric cancer and duodenal tumors at the same time. MC can cause pregastric papillary carcinoma in all animals after 3 months, and can cause gastric cancer in gastric adenocarcinoma after 7-8 months, with a carcinogenic rate of 85%-100%. [Model Evaluation and Application] In order to study the etiology of gastric cancer, the most effective method is to induce gastric cancer with drug inducers. This allows us to further verify various suspicious carcinogens and cancer-promoting factors, and to clarify and explore the etiology of gastric cancer, the mechanism of action of anticancer drugs and their screening. Gastric cancer induced by chemical carcinogens is suitable for the etiology, pathological process, biological behavior, tumor immunity and anti-tumor drug screening of gastric cancer.

　　The sensitivity of animals of different species, genders and ages to carcinogens varies greatly. This directly affects the cancer induction rate and modeling time. Single-factor mutagenesis lasts for a long time, the incidence of cancer is low, and the method of administration, time and drug concentration greatly affect the rate of tumor formation. The rat gastric cancer model induced by multiple factors is closer to the etiology of preclinical lesions, with shorter cycles and higher induction rates. However, due to the high mortality rate of multi-factor attackers, special attention should be paid to the concentration of mutagens such as MNNG during the experiment.