药理学,实验动物 z-bo 2020-07-27 1446

　　Mice, rats, guinea pigs and rabbits are common in pharmacological research.

　　(1) Mice are commonly used animals in acute toxicity studies, weighing 18-22 g, and hermaphrodite. Inject 5-10 animals into the tail vein or peritoneal cavity each time and inject a fixed dose of liquid medicine to check for side effects (convulsions, quadriplegia, gait disturbance, erect hair, respiratory depression, etc.) or death. Do it. Observe for 24 to 48 hours. After calculation, the adult body weight is 50 kg, and the mouse body weight is 20 grams. In other words, humans weigh about 2500 times heavier than mice. For example, for a human dose of 2 ml, a 0.5 ml mouse will not cause death, which means that the maximum tolerated dose for mice is more than 625 times the human dose. The higher the multiple, the lower the toxicity. It is generally believed that the maximum tolerated dose of mice calculated by body weight is more than 100 times the human dose. It is safer and can be used clinically.

　　(2) Mice can be selected for subacute and chronic toxicity studies. This method is basically similar to acute toxicity studies, but the dose is lower. Based on body weight, mice are given 20 to 50 times the human dose orally or intraperitoneally every day, and observation is continued for 1 to 8 weeks. The chronic toxicity test takes 3 to 6 months. Observe changes in body weight, food intake, and water intake for any other side effects or death (including visual inspection of internal organs or tissue biopsies). If necessary, perform clinical examination of blood, liver and kidney function. Rats are also commonly used in this experiment. (3) Determine the half-lethal dose. The half-lethal dose is called LD50, which refers to the dose that causes half of the death of experimental animals. Due to individual differences, animals of the same species may or may not die when given the same dose of drugs. When showing drug toxicity, LD50 is more sensitive and accurate. It is usually expressed in mg/kg (drug dose/body weight). In clinical applications, 1/5 to 1/10 LD50 is usually used, and trials to observe toxicity and efficacy are started. Try gradually from small to large until it becomes unbearable. Find a satisfactory treatment effect and low toxic dose, and conduct detailed observations. Male and female mice weighing 18 to 22 g are usually used to determine LD50. Each experiment usually requires 60-60 mice. The route of administration is the same as the clinical application such as oral, intraperitoneal injection and intravenous injection. The dose per mouse is approximately 0.5 ml. Depending on the effect of the drug, it is usually observed for 1 to 4 hours or 24 to 72 hours, and death is the main indicator. (4) Allergy test. Six guinea pigs weighing 250-350 g were injected intraperitoneally with 0.5 ml every 6 days for a total of 3 injections. After that, the mice were divided into two groups, and 1 ml of stock solution was injected from the jugular vein on the 14th and 21st days of the first injection. If an allergic reaction occurs, within a few minutes after the injection of the drug, the guinea pig will become irritable, have difficulty breathing and immediately suffocate to death.

　　(5) Pyrogen check Pyrogen is a toxin produced by bacteria. If the injection contains pyrogens, heat will be generated. The animal used to confirm the pyrogen is a rabbit, usually three animals weighing 1.5 kg or more. The anal temperature is measured 3 times before injection and the average is taken (the normal body temperature of a rabbit is 38.5-39.6°C). ). After that, the drug was injected into the ear vein (1-2 ml/Kg), and the body temperature was measured 1, 2, and 3 hours after the injection. If the body temperature of the three rabbits does not exceed 0.6°C, then they are qualified and pyrogen-free.