动物造模,糖尿病肾病动物模型 z-bio 2023-01-17 850

　　1. The rat model of streptozotocin-induced diabetic nephropathy (1) Reproduction method Wister experiment excised the right kidney of the rat. Two weeks later, 35 mg/kg body weight of streptozotocin (STZ) was injected through the dorsal penis vein. Two days later, the rat’s tail was cut and blood was collected to determine that the blood glucose level exceeded 2 g/L. During the entire experiment, The blood glucose level of the rat remained constant. Has stable, moderate hyperglycemia. After 24 hours, the proteinuria of rats increased significantly at 4 weeks, and showed a gradual increase trend over time. At 5 months, urine output, mean arterial pressure, renal vascular resistance and renal filtration rate all increased significantly. The pathological examination of the kidneys showed that kidney hyperplasia and hypertrophy, heart weight ratio, kidney weight ratio and glomerular sclerosis index increased significantly. (2) Model characteristics: In experimental rats injected with low-dose STZ, unilateral kidney was removed, which accelerated the kidney damage process of diabetic nephropathy. Due to lack of external insulin therapy, rats were continuously exposed to hyperglycemia. Because it is the blood sugar level, it will accelerate the damage to the kidneys. (3) Comparative medicine Type I diabetes is one of the chronic diseases that seriously threaten human health, and its incidence is still rising. Diabetic nephropathy is the main cause of end-stage renal disease. Currently, there are two main problems in establishing type 1 diabetic nephropathy to maintain moderate to high blood sugar. One is that the onset of kidney damage is very slow, and the other is the need to use high doses of STZ to control exogenous insulin. Metabolic disorders. The model in this experiment can continuously and reasonably maintain high blood glucose levels, which helps humans to study diabetic nephropathy.

　　2. Rabbit diabetic nephropathy model induced by high-fat and high-sugar diet

　　(1) Reproduction method A New Zealand male rabbit weighing about 2 kg was provided with a high-fat, high-sugar diet containing 10% lard and 37% fat with% sucrose, and each animal consumed about 75 grams of feed per day. Before feeding the high-fat and high-sugar feed and every two months during the feeding, the blood fasted from the animal’s ear artery overnight is used to measure blood lipids, blood sugar and insulin. Before the animals were sacrificed at the end of the fourth month of feeding, the body weight, 24-hour urine protein and creatinine clearance (CCr) of the two groups were measured. After the model animals were sacrificed, the concentration and activity of nitric oxide were measured. Measure the amount of nitric oxide synthase in its plasma and kidney tissue. At the same time, collect kidney specimens of model animals, fix them in a fixative, and perform normal tissue sectioning, HE staining and pathological blood observation under an optical microscope.

　　(2) Model characteristics: After feeding the model animals with a high-fat and high-sugar diet for one month, their plasma blood glucose and insulin readings were higher than those of pre-feeding and plasma blood, and were significantly higher. Blood sugar and insulin gradually increase with the increase of feeding time. The body weight/body weight of the animal’s kidneys, urine protein, creatinine clearance and arterial blood pressure were significantly higher than before feeding. Compared with before feeding, NOS active animal model and plasma or kidney tissue levels of NO increased significantly. Microhistopathological observations showed that the glomerular mesangium in the renal cortex of the model animals was slightly hyperplastic, and the capillary diameter was larger than the width of the mesangium, and it was distributed in segments; the mesangium was located near the medulla oblongata and showed moderate hyperplasia. The membrane is larger than the diameter of the capillaries, the capillaries are easy to aggregate or spread and distribute, compress the inner cavity of the capillaries and form KW nodules and fibrin caps. The pathological changes of glomeruli in kidney tissue tend to gradually deteriorate. (3) Comparative medicine Diabetic nephropathy (diabetic nephropathy, DN) is one of the common complications in clinical practice of diabetic patients. The pathological change is glomerular sclerosis, and its etiology is mainly related to abnormal renal hemodynamics and hyperglycemia. Activation of aldose reductase C (PKC) and other factors. Abnormal endothelial diastolic function caused by abnormal NO metabolism in diabetic patients is closely related to the above reasons. This model uses a method of feeding New Zealand rabbits with a high-sugar and high-fat diet, which may lead to a continuous increase in animal blood sugar and insulin. After one month of feeding, the average blood glucose level of the model animals was close. It reached 6.7 mmol/L and exceeded 6.7 mmol/L within three months. Previous studies have shown that the initial kidney weight/body weight of the rat diabetes model established with streptozotocin (STZ) is higher than that of normal animals, resulting in a significant increase in the volume of the kidney and glomerulus in the early stage of experimental diabetes. The model replicated in this way has increased kidney weight/body weight ratio, proteinuria, NO level and NOS activity, as well as increased blood glucose and insulin levels in model animals. With urine protein, CCr was significantly higher than normal. It belongs to a rat model of diabetes induced by STZ and also belongs to early diabetic nephropathy.