疾病动物模型 z-bio 2021-03-11 248

　　(1) Animal model of streptozotocin-induced diabetes

　　[Modeling mechanism] The chemical name of streptozotocin (STZ) is 2-desoxy-2-(3-methyl-3-nitrosoureido)-d-glucopyranose, which is a fermentation product of Streptomyces achromaticus and its structure The nitrosourea is a cytotoxin, which selectively destroys the pancreatic islet β cells of some species of animals, and can cause diabetes in experimental animals such as monkeys, dogs, sheep, rabbits, rats, and mice. It is currently used The most extensive chemical inducer of diabetes in animal models. STZ damages β cells through free radicals (such as CH3) and impairs the synthesis of insulin in the cells, resulting in insulin deficiency. When STZ induces and prepares a type 1 diabetes model, multiple low-dose injections can effectively simulate the course and pathogenesis of diabetes and reduce animal mortality, so it is currently used more frequently.

　　[Modeling method] Streptozotocin is easily soluble in water, and its aqueous solution is extremely unstable at room temperature and can be decomposed into gas within a few minutes, so its aqueous solution should be prepared and stored under low temperature and pH 4 conditions. It can also be used to make a 2% STZ solution with 0.05mol/L citric acid (pH4.5) before injection, and use it fresh. The dose of STZ varies with the species and species of experimental animals. The susceptibility of different species of animals to the β-cytotoxicity of streptozotocin is quite different. Dogs, rats and mice are mostly selected for testing. Rats are the most commonly used. The dose of STZ in rats with diabetes is 40～75mg/kg (intravenous injection or intraperitoneal injection). Regardless of gender, fasting is required for 24 hours before the experiment. Mice are less sensitive to this drug, and the usual dose is 100-200mg/kg (intravenous or intraperitoneal injection). 72 hours after STZ injection, blood sugar can rise steadily, and the animal has more than three symptoms (polyphagia, polydipsia, and polyuria). At this time, the predicted blood glucose level above 11.1mmol/L can be used. Injecting a small dose of STZ (35-40mg/kg) to mice for 5 consecutive days can cause insulitis after 1 to 2 weeks, and males are more sensitive.

　　[Model features] After injection of streptozotocin in monkeys, dogs, rats and mice, the changes in blood glucose levels can also be divided into three phases: the early hyperglycemia phase, which lasts about 1 to 2 hours, and the hypoglycemia phase , Lasting about 6-10 hours and after 24 hours, a stable hyperglycemia phase, that is, the diabetic phase, appears. After injection of STZ, the islets of the pancreas showed obvious pathological changes. β cells show varying degrees of degranulation, degeneration, necrosis and regeneration changes. Different from alloxan diabetes, the diabetic hyperglycemia and ketosis caused by streptozotocin are milder.

　　【Model evaluation and application】This model is suitable for the study of diabetes pathogenesis, pathophysiological changes and effective drug treatment. It is commonly used in drug screening and pharmacodynamic research of effective Chinese medicines for the treatment of diabetes.

　　(2) Alloxan Diabetes Animal Model

　　[Modeling mechanism] Alloxan (alloxan) is a β-cytotoxic agent that selectively damages pancreatic β cells in a variety of animals by generating superoxide free radicals, causing cell DNA damage, and activating poly ADP ribosomal synthase (poly(ADP-ribose) synthetase) activity, which reduces the content of coenzyme Ⅰ (nicotinamide adenine dinucleotide, NAD), resulting in impaired mRNA function and decreased insulin before β-cell synthesis, leading to insulin deficiency and experimental diabetes.

　　【Molding method】Alloxan is easily soluble in water and weak acid. Its aqueous solution is unstable and easily decomposes into alloxan and becomes invalid. Therefore, it should be prepared before use. The dosage varies according to the sensitivity of the animal and the route of administration. Intravenous injection, intraperitoneal injection and subcutaneous injection of alloxan can cause diabetes, and intravenous injection is the most commonly used. The safety range of alloxan is relatively large, and its half lethal dose is 4 to 5 times that of diabetes. Currently, one intraperitoneal injection of 150 to 200 mg/kg or intravenous injection of 40 to 100 mg/kg is most commonly used.

　　【Features of the model】After injection of alloxan, the blood glucose level of the animal usually changes in three phases: the initial hyperglycemia appears after 2 to 3 hours after the administration, and the hypoglycemia phase appears after 6 to 12 hours, and the animal appears convulsions, 24 Hours later, it is usually a period of persistent hyperglycemia, β-cells show irreversible necrosis, and diabetes occurs. The severity of alloxan diabetes mainly depends on the dose of alloxan and the type of animal. Large doses of alloxan can destroy all β cells, causing severe diabetes and death due to ketoacidosis.

　　【Model evaluation and application】This model is suitable for the study of diabetes pathogenesis, pathophysiological changes and effective drug treatment. It is commonly used in drug screening and pharmacodynamic research of effective Chinese medicines for the treatment of diabetes.