Animal model of chronic renal failure
Animal model of chronic renal failure
Chronic renal failure is a common destination in the late stage of various primary or secondary renal diseases, which is a group of clinical syndromes characterized by progressive destruction of renal units and thus disruption of renal excretory function, internal environmental stability and endocrine function. From the analysis of clinical data, it is found that no matter what the primary cause is, as long as the kidney is damaged to a certain extent, even if the primary disease is removed or terminated, the diseased kidney will continue to be progressively destroyed, and finally enter the terminal kidney.
Principle
Depending on the experimental method, the corresponding principles differ:
Basic principles of animal models of chronic renal failure: Since Tuffier first established the rat partial nephrectomy model in 1889, there have been more than 100 years of history, and dozens of animal models of chronic renal failure have been established, including mice, rats, guinea pigs, rabbits, cats, dogs, pigs, sheep, monkeys and so on, with the common point of reducing renal units. The common denominator is the reduction of renal units, and all of these models can simulate to some extent the development of chronic renal failure in some human chronic kidney diseases, and all of them have their own limitations. Currently, physical methods are often used to reduce or destroy renal tissues; nephrotoxic drugs are used to destroy renal tissues; immunological methods are used to destroy renal tissues and other methods are used to destroy renal tissues in order to replicate animal models of chronic renal failure. Appliance The common application fields of animal models of chronic renal failure are as follows: the above models can be used to study the occurrence and development mechanism of chronic renal failure and its prevention and treatment research. However, the destruction of renal tissue by physical methods is easy to quantify and the success rate of modeling is high, but the difference with the common clinical causes is large; the destruction of renal tissue by immune methods is not easy to control the extent of the disease, and the success rate of modeling is low, but it is similar to the natural clinical course of the disease. Operation method Animal model of chronic renal failure Principle Chronic renal failure is a common destination in the late stage of various primary or secondary renal diseases, which is a group of clinical syndromes characterized by progressive destruction of renal units and thus disruption of renal excretory function, internal environmental stability and endocrine function. From the analysis of clinical data, it is found that no matter what the primary cause is, as long as the kidney is damaged to a certain extent, even if the primary disease is eliminated or terminated, the diseased kidney will continue to be progressively destroyed, and finally enter the terminal kidney. Since Tuffier first established the rat partial nephrectomy model in 1889, there have been more than 100 years of history, the animal models of chronic renal failure (animal models of chronic renal failure) dozens of kinds of animals including mice, rats, guinea pigs, rabbits, cats, dogs, pigs, sheep, monkeys, etc., and the common point is to make the renal unit reduction. The common denominator is the reduction of renal units, and all of these models can simulate to some extent the development of chronic renal failure in some human chronic kidney diseases, and all of them have their own limitations. Currently, physical methods are often used to reduce or destroy renal tissues; nephrotoxic drugs are used to destroy renal tissues; immunological methods are used to destroy renal tissues and other methods are used to destroy renal tissues in order to replicate animal models of chronic renal failure. Materials and Instruments Subjects: Move The basic process of the animal model of chronic renal failure can be divided into the following steps: (1) Partial (5/6) nephrectomy method: There is a transient increase in plasma urea nitrogen and muscle tincture at 1 week after surgery, which is called acute renal failure or acute decompensated period, and plasma urea nitrogen and creatinine concentrations return to normal at 2~3 weeks after surgery. The chronic renal failure stage begins gradually at 4 weeks after surgery, with gradual and sustained increase in plasma urea nitrogen and creatinine concentration, anemia, hypertension, proteinuria, glomerular hypertrophy, and tethered membrane proliferation. If the surgery is done once, the mortality rate of animals in the postoperative acute renal failure stage is high. The advantage of this model is to create a simple overload model of the residual renal tissues while keeping the residual renal tissues relatively normal, discharging the influence of various primary renal disease causative factors themselves on the fate of the residual renal units, and simplifying the influencing factors so as to facilitate the observation of a series of changes and their mechanisms occurring in the 'normal' residual renal units in the event of loss of most of the renal tissues. (2) Electrocautery cauterization, liquid chlorine freezing or ligation of the renal arteries method: After electrocautery, the weight of the animal increases slowly, the urine flow is higher in the first 30 days and increases more after 4 months, oliguria or anuria occurs a few days before death, the serum creatinine increases significantly, and the endogenous creatinine clearance decreases progressively, the chronic renal failure rats induced by this method can survive for 4-6 months. 15 days after the drug, plasma urea nitrogen and creatinine concentrations increased significantly; the epithelial cells of renal proximal tubules were swollen and degenerated, and there were no obvious lesions in the liver and duodenum; 45 days after the drug, plasma urea nitrogen and creatinine concentrations increased more significantly, and the increase was still progressive after the drug was discontinued; in addition to renal tubular epithelial cells, the renal mesangium was infiltrated with single nucleated inflammatory cells, and there were increased numbers of nucleated cells in glomeruli; there were no abnormal findings in the liver and duodenum. At 125 days after administration, renal tubular lesions disappeared, the number of glomerular nucleated cells increased even more, glomerular hypertrophy, some glomerular fibrosis, and the renal interstitium was still infiltrated with single nucleated inflammatory cells. After stopping cadmium chloride, the renal damage is still progressively aggravated. (1) Anti-glomerular tethered cell nephritis method: Generally 1~2 months, the animal that is the emergence of blood creatinine and urea nitrogen elevation and other biochemical changes and clinical manifestations of chronic renal failure, renal pathology can be seen significant glomerulosclerosis, some glomeruli can be seen in the formation of crescent, the renal interstitium can have inflammatory cell infiltration and fibrosis. (2) Anti-glomerular basement membrane nephritis method: Immunopathological examination of the kidney reveals a large amount of IgG along the GBM with continuous linear deposition. Plain light microscopy reveals widening of the glomerular mesangial zone, proliferation of mesangial cells and endothelial cells, thickening of the basement membrane, glomerulosclerosis, and inflammatory cell infiltration and fibrosis in the renal interstitium. (3) Chronic serous nephritis method: Generally, nephrotic syndrome and azotemia appear in rabbits after 1~3 months. The renal lesions are complex, with irregular granular deposits of alloantigen, autoimmune globulin and complement on the glomerular basement membrane in the early stage, and mild proliferation of glomerular mesangial cells; in the late stage, the glomerular basement membrane is significantly thickened and deformed, and the glomerular mesangial cells and epithelial cells proliferate markedly, and there is often the formation of crescent bodies. The disadvantage of this model is that the individual difference of animals is large, and the mortality rate is high. Caveat Physical methods to reduce or destroy renal tissue law: the shortcomings of this model are the need for appropriate surgical sites, instruments and skilled operators, and the long lead time for model preparation. For more product details, please visit Aladdin Scientific website.
① Rats.
Experimental reagents:
① Physiological saline.
1 . Physical methods to reduce or destroy the renal organization method
2 . Nephrotoxic drugs destroying the renal tissue method
3 . Immunological method to destroy renal organization