Establishing method of chronic kidney disease angiosteosis experiment model

Abstract

The invention belongs to the field of nephrology, and relates to a chronic kidney disease angiosteosis experiment model and a making method thereof. The chronic kidney disease angiosteosis experiment model is established by using C57BL / 6 mouse molding through cooperation of combination of adenine and vitamin D with a high-phosphorus and low-protein diet intervention mode. The making method has the advantages of short modeling time and good stability; and the established chronic kidney disease angiosteosis experiment model can be further used to screen drugs for treating chronic kidney disease angiosteosis and research mechanisms of the drugs.

Description

technical field [0001] The invention belongs to the field of nephrology and relates to a method for establishing an experimental model of vascular calcification of chronic kidney disease. Background technique [0002] Currently, the medical community recognizes that CKD-MBD (chronickidney disease-mineral and bone disorder) refers to a systemic disorder of mineral and bone metabolism caused by chronic kidney disease. Among them, vascular calcification is a common complication of CKD. Patients with CKD at various stages Calcium and phosphorus metabolism disorders existed in varying degrees, and the resulting vascular calcification was an independent risk factor for the death of late cardiovascular events in CKD patients. [0003] Generally, in the prior art, the 5 / 6th resection rat kidney model and the adenine rat nephrotoxicity model are often used to conduct research on vascular calcification caused by renal failure. In the above two models, experimental animals after acute...

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Problems solved by technology

The 5 / 6th resection rat kidney model is more classic, and the glomerular damage that occurs is similar to human focal segmental glomerulosclerosis. Generally, the blood creatinine and blood urea nitrogen in the operation group are obvious after 8 to 12 weeks. Increased, hypocalcemia, hyperphosphatemia, showing typical symptoms of chronic renal failure, and cardiovascular and renal bone diseases such as vascular calcification, decreased bone density and other complications of chronic renal failure; but this model has the following shortcomings: ( 1) It is necessary to establish a model by one-step or two-step surgery, which increases the chance of anesthesia accident and surgical infection; (2) the modeling cycle is long, usually more than 18 weeks; in contrast, the adenine The mouse nephrotoxicity model has attracted more attention in recent years because of its simplicity and high survival rate. Compared with the 5 / 6th nephrectomy rat model, it has more rapid and severe nephropathy progression, hyperparathyroidism and arterial calcification, and is usually given After 4 weeks of diet containing 0.75% adenine, CKD symptoms appeared, manifested as secondary hyperparathyroidism, parathyroid hyperplasia, a sharp increase in parathyroid hormone in the blood, serious disorders of calcium and phosphorus metabolism, and bone regeneration. The absorption is enhanced, and the calcification of the aorta, coronary artery and other soft tissues is formed; the aortic calcification mainly appears in the media, which is very similar to the typical clinical arterial calcification of chronic dialysis patients, but this model also has two major shortcomings: ( 1) Because the rats eat freely, the amount of adenine intake varies greatly, and the individual models vary greatly; (2) This model will cause severe weight loss in rats, and even the body weight will drop by almost 50% after modeling. %

The above defects are obviously not conducive to drug research and screening. Based on this, Terai et al. improved the nephrotoxicity model of adenine rats, and administered 600mg / kg / d adenine to the rats, and acute kidney injury was caused after 10 days, and no obvious Weight loss; however, the biggest disadvantage of the established model is the low incidence of vascular calcification, only about 12.5% ​​at 8 weeks, although it exhibits nephrotoxicity and bone changes

[0004] To sum up, the current animal models of vascular calcification of chronic kidney disease are all made of rats, and the modeling rate is generally not high; and because rat experiments require a large amount of drugs, a large experimental space, and a large amount of labor, the industry does not recommend the use of vascular calcification. Screening and evaluating anti-vascular calcification drugs in this type of animal model is not optimistic

[0005] At the same time, based on experimental mice limited to gene knockout models, such as: apolipoprotein E-deficient mice, osteopontin (OPN)-deficient mice, matrix Gla protein (MGP)-deficient mice, osteoprotegerin (osteoprotegerin, OPG) )-deficient mice, etc.; although the gene knockout method can eliminate the side effects and complex factors that accompany diet and drug-induced vascular calcification, its preparation process is complicated, time-consuming, and costly, so it cannot be widely used

[0006] At present, there are no reports about adenine or 5 / 6Nx ablation-induced vascular calcification in mice at home and abroad, which may be related to the difficulty of nephrectomy in mice or the higher mortality rate after administration

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