动物造模,药效评价,糖尿病视网膜病变 z-bio 2024-07-08 408

　　[Modelling mechanism] In diabetes, the retina is exposed to high concentration of plasma glucose, and intracellular free glucose accumulates, activating aldose reductase, the key enzyme of sorbitol metabolism. The production of sorbitol is accelerated, and sorbitol accumulates in pericytes of retinal capillaries, M ü ller cells of retina membrane, and some special cellular components. The accumulation of sorbitol in the walls of capillaries leads to long-term high osmotic state, which stimulates progressive thickening of the basement membrane and disrupts its scaffold function, cell attachment, and filtration function. This can cause peripheral cell death, formation of microaneurysms, and changes in exudation and bleeding.

　　【 Modeling Method 】 Streptozocin (STZ) induced animal model: Streptozocin was dissolved in 0.1 mmol/L citrate sodium buffer in an ice bath. 2.1g of citric acid was added to 100ml of double distilled water to form liquid A. 2.94g of trisodium citrate was weighed and added to 100ml of double distilled water to form liquid B; Mix 28ml of solution A and 22ml of solution B, dilute the mixture with double distilled water to 100ml to obtain citric acid buffer, measure the pH to about 4.5, and place it in an ice bath for later use. Mix with STZ to form a 10g/L STZ-DM solution and inject it intraperitoneally at a dose of 55mg/kg. Rats were fasted with water for 12 hours before administration. The entire process is sterile, and eating is resumed 30 minutes after injection. Measure blood glucose by collecting tail blood 72 hours later. The 10 week STZ-DM Sprague Dawley rat can serve as an animal model close to early human BDR for experimental studies related to DR.

　　【 Model Characteristics 】 In the early stages of successful modeling, ERG began to change, and the amplitude of ERG showed a trend of first increasing and then decreasing; OPs waves first exhibit an extension of the O2 peak value, followed by a decrease in the amplitude values of each sub wave of OPs. Pathological observation shows thickening of the basement membrane of capillaries, increased finger like protrusions and phagocytic vesicles in endothelial cells; Mitochondrial swelling, cristae shedding, and vacuolar degeneration in pericytes, bipolar cells, and ganglion cells; The number of outer membrane discs of retinal photoreceptor cells decreases and the gap widens; Vascular tortuosity and capillary dilation. Ultrastructural display: Lanthanum particles infiltrate into all layers of the retina (Figure 12-3); Retinal capillary endothelial cell proliferation and basement membrane thickening.

　　[Model evaluation and application] The STZ induced retinal animal model of diabetes can simulate the human insulin dependent diabetes model by inducing the pancreas to produce a large number of oxygen free radicals to cause β cell damage, leading to a decrease in blood insulin and an increase in blood glucose. This molding method is simple, economical, has good repeatability, and a high molding rate. So at present, most of the induced diabetes retinal animal models are established by STZ method, but it is worth noting that the established diabetes animal models are not all prone to diabetes retinopathy. The STZ induced rat model takes 1-3 days to establish and the observation period is usually 1-6 months. It is necessary to observe in depth whether all animals with high blood sugar in the short term produce true DR.