【Animal Modeling】-Nephrotoxic and Chronic Renal Failure Animal Model

  [Modeling mechanism] Adenine produces 2,8-dihydroxyadenine through the action of xanthine oxidase deposited in the glomerulus and renal interstitium, forming a foreign body granulomatous inflammation, and blocking the lumen of the renal tubules. The renal tubules react and cause cystic dilation. As the disease progresses, the loss of a large number of nephrons can lead to kidney failure.

  [Model creation method] Male Wistar rats weighing 200±30 g were selected and fed with a normal diet for 1 week. Dissolve 1 g of adenine in 40 ml of normal saline, prepare a suspension with a concentration of 2.5% at a dose of 200 mg/(kg·d), and give it by oral tube every day for 24 consecutive days. After the experiment, the animals were sacrificed and the kidney tissues were fixed with 10% formaldehyde, embedded in paraffin, sectioned, stained with H&E, and histopathologically examined and photographed by optical microscopy.

  [Model Features] Renal failure is a typical sign. The rats in the model group showed increased days of adenine, chills in limbs, curled back, lethargy, hair loss, edema and loose stools, kidney "large white kidney", reduction of red blood cells and hemoglobin. , BUN and Cr are elevated high, low calcium, high phosphorus, mainly the biochemical changes of chronic renal failure. The pathological changes of the renal tubules are obvious. The adenine-induced CRF model has renal tubular obstruction, and the pathological changes are mainly renal tubular damage. The kidneys are obviously hypertrophy. The two kidneys are gray-white with granular surfaces. It is not easy to separate the adhesion between the kidney capsule and the kidney parenchyma, and the cut surface is blurred. Under an optical microscope, the glomeruli were reduced in number, atrophy, and their shape was basically normal. The renal tubules expand into cysts, there are many crystals deposited in the renal cortex, and there are foreign body giant cells around the crystals. Many renal tubules are destroyed and atrophy disappears. Inflammatory cell infiltration, interstitial fibrosis is obvious.

  [Evaluation and application of the model] The method of the rat adenine CRF model is simple and controllable. According to the size of the adenine dose and the length of feeding time, it can be a model of mild, moderate and severe renal failure. The course of the disease is stable and suitable for long-term administration. High success rate, easy to promote and easy to apply. Pathological observations show that the main feature of this model is the destruction of renal tubules, and new drug models that restore renal tubule function often produce positive results. According to reports, the model also lowered the animal's basal body temperature, contraction of testicular tissue and sperm reduction. Since this model has been mainly used as a "Kidney Yang Deficiency" model in recent years, this model is more suitable for new anti-renal insufficiency drugs with renal hyperthermia.