动物造模,肾病 z-bo 2022-09-21 505

　　Sclerosing glomerulonephritis is the end stage of many types of glomerulonephritis, rather than an independent pathological type of glomerulonephritis. The pathological changes are characterized by extensive glomerulosclerosis, renal tubular atrophy and loss, and interstitial fibrosis.

　　[Modeling mechanism] Doxorubicin is an anthracycline antibiotic containing quinone, which is reduced to semiquinone free radicals in the kidney, and induces oxidative stress to produce reactive oxygen species, which leads to lipid production in glomerular epithelial cells . possible. Peroxidation can change the glucose metabolism of glomerular epithelial cells, causing swelling of glomerular capillary endothelial cells and podocytes, loss of foot process fusion, thickening of basement membrane, proteinuria and high lipid content in animals. Symptoms of blood and hypoproteinemia, hyperazotemia, and low renal function can develop into chronic sclerosing nephropathy similar to humans. Unilateral nephrectomy can directly reduce nephrons, increase renal blood flow, increase glomerular filtration rate of residual renal tissue, increase glomerular pressure, renal parenchymal cell infiltration, urine protein and blood pressure. increase. The height is high and eventually leads to glomerular sclerosis. Unilateral nephrectomy and tail vein injection of high or low dose doxorubicin can be replicated in typical models of early and late glomerulosclerotic nephropathy.

　　[Modeling method]

　　1. During the experiment, male Sprague Dawley rats (body weight 180-220 g) were adaptively reared for one week. After anesthesia with 1.5% pentobarbital (50 mg/kg), the left kidney was removed by aseptic surgery. After the operation, the animals were randomly divided into high-dose and high-dose groups. On the 8th day, the low-dose group was injected with adriamycin (5 ml) through the tail vein. /kg), 0.5 ml of saline was injected into the tail vein on day 35, and doxorubicin (3 mg/kg) was injected into the tail vein of the high-dose group on day 8. On day 35, doxorubicin (2 mg/kg) was injected into the tail vein for the second time. The animals were sacrificed at the 8th week, and blood samples and kidneys were taken for corresponding tests. 2. Index detection can detect 24-hour urine output, urine protein content, BUN, Cr, total protein, albumin, cholesterol, triglycerides. H&E, PAS and Masson were used to stain histopathological sections of the kidney to observe the diameter of the capillary opening, glomerular sclerosis index and matrix growth area ratio, and finally observe the ultrastructure of the kidney with a transmission electron microscope. .. [Characteristics of the model] In the 8th week, both the high-dose group and the low-dose group showed increased urinary protein excretion, increased blood lipids and decreased renal function. In the high-dose group, the glomerular sclerosis reached more than 80% under the light microscope, which was diffuse, of which 25%-50% showed glomerular sclerosis, and the foot processes of glomerular visceral epithelial cells were extensively fused or disappeared; renal tubular disease was severe , Renal tubular epithelial cells swelled, granular degeneration, necrosis and shedding into the small lumen, showing a large number of protein casts; interstitial fibrosis and multiple inflammatory cell infiltration; glomerular sclerosis in the low-dose group showed local and Partially distributed, the kidney is small, the glomerulus is enlarged, and the kidney capsule is enlarged. About 50% of glomerular sclerosis varies in degree, and about 10% of glomerular sclerosis. There are obvious fibrosis and local inflammatory cells in the matrix. The low-dose group had early pathological changes in glomerulosclerosis, while the high-dose group had middle and late pathological changes. [Model evaluation and application] Glomerulosclerosis is an irreversible pathological change that develops to the end of various glomerular lesions and is the main pathological basis of renal failure. The first expression is local, and the latter expression is a diffuse spherical distribution. The currently used animal models of glomerulosclerosis mainly include total nephrectomy, renal artery ligation surgery models and drug models, such as adriamycin, puromycin, and daunorubicin. The animal model of glomerulosclerosis caused by adriamycin is a stable glomerulosclerosis model with the characteristics of chronic progressive nephropathy, which is very similar to human progressive nephropathy and better than sclerosing animals.