[Modeling mechanism] Type 2 diabetes is the result of the combined effect of genetic factors and environmental factors. In addition to elevated blood sugar, it is often accompanied by abnormal blood lipids. At present, the most widely used type 2 diabetes model is the drug method. Small doses of STZ were injected into rats, which caused mild damage to pancreatic islet β cells, which caused most animals to produce impaired glucose tolerance. On this basis, feeding animals with high-calorie diets caused animal obesity, accompanied by hyperlipidemia and hyperinsulinemia. And insulin resistance. Or feed the rats with a high-sugar and high-fat diet for one month, and then inject a small dose of STZ (25mg/kg body weight) into the intraperitoneal cavity after insulin resistance is induced to induce hyperglycemia. High-sugar foods can cause hyperinsulinemia in rats, and high-fat foods can reduce insulin secretion and glucose tolerance in the rat pancreas. The mechanism of high-sugar and high-fat diet inducing insulin resistance may be due to the increased levels of serum triglycerides and free fatty acids (FFAs). FFAs inhibit sugar storage through multiple pathways such as the sugar-lipid cycle and insulin signaling. In addition, long-term hyperglycemia can imbalance the production and clearance of antioxidants in the body, cause tissue cell apoptosis and cause extensive damage, reduce insulin sensitivity, and ultimately lead to the occurrence of insulin resistance. In the case of insulin resistance, give a small dose of STZ. It can lead to an imbalance of the body's blood sugar homeostasis and eventually cause diabetes.
[Modeling method] Choose male or female Wistar rats, weighing about 250g, and inject 25-30mg/kg of STZ (intravenous injection, the preparation method is the same as before), measure the glucose tolerance after 2 to 3 weeks, and select those with abnormal glucose tolerance. High-fat feed (basic feed mixed with sucrose, refined lard, fresh eggs, etc., contains 15%-18% protein, 51%-54% carbohydrates, 22%-25% fat, and 20.08kJ/g of calories. ), the animals are fed individually to ensure the food intake of each animal for 10 to 18 weeks. One month later, the 24-hour food intake, body weight, blood pressure, non-fasting blood glucose, plasma insulin, blood triglyceride and cholesterol levels were measured, and insulin inhibition test was performed to evaluate insulin sensitivity.
[Model Features] Low-dose STZ and high-fat diet feeding are necessary conditions for the formation of this rat model. The experiment period is short and the cost is low. Compared with the type 2 diabetes model induced by high-energy feed alone, the induction time is significantly shortened, and compared with the type 2 diabetes model induced by simple STZ injection, the modeling rate is significantly increased. At the same time, the symptoms and symptoms of the type 2 diabetes model induced by this method are The pathogenesis is very similar to human type 2 diabetes, so it is a good way to establish experimental animal models of type 2 diabetes.
【Model evaluation and application】The rat type 2 diabetes model has the characteristics of moderate hyperglycemia, hyperlipidemia, hypertension, insulin resistance, and high success rate. It simulates the pathogenesis, pathological process and clinical features of diabetes to a certain extent, and is an ideal model for studying the vascular complications of type 2 diabetes. It can be used to study the pathogenesis and prevention methods of diabetes.