【Animal Modeling - Pharmacological Evaluation】 - Adenosine induced Chronic Renal Failure Rat Model

  1. Modeling material animals: Adult male SD rats weighing 300-360g; Drug: Adenosine.

  2. The modeling method involves preparing 1ml of adenine suspension at a daily dose of 200mg/kg, and administering the drug to rats by gavage at regular intervals. The total cumulative dose is 1.5g/animal, and the entire modeling process lasts for 24 days. Administer once a day from day 1 to day 12, and administer every other day after day 12. On the 30th day after the start of drug administration, all animals were euthanized, blood samples were taken for biochemical testing, and kidney tissue was taken for histopathological examination under light microscopy.

  3. Modeling principle: Adenine is hydrolyzed by a series of enzymes in the animal body to form uric acid. When the concentration of uric acid in the blood exceeds 500 μ mol/L (8.5mg/dl), urate will precipitate crystals and deposit in the renal tubules and interstitium, forming urate foreign body granulomatous inflammation and blocking the renal tubules, causing the corresponding renal tubules to expand in a cystic manner. As the disease progresses, a significant loss of nephrons occurs, leading to renal failure.

  4. After modeling, the experimental group animals began to experience polyuria, excessive drinking, and mental fatigue from the 12th to the 15th day of administration. They gradually developed symptoms such as reduced food intake, weight loss, dry fur, pale earlobes, pale red eyes, squinting, swelling around the eyelids, wet and cold tails, reduced activity, vertical hair, curling up, polyuria, and wet fur around the external genitalia.

  5. After modeling, biochemical and pathological changes were observed, and renal function tests showed an increase in both serum creatinine and urea nitrogen, which was significantly different from the normal group. The total carbon dioxide (TCO2) in plasma significantly decreased, while the anion gap (AG) in plasma increased.

  Renal pathological light microscopy examination: In the experimental group of rats, the healthy glomeruli accounted for about 25%, and most of the glomerular capillaries in the renal cortex area had thickened basement membranes, increased mesangial cells, and lobulated glomeruli. In addition to a large number of foreign body granulomas and nodules, the main lesions were inflammation of the renal tubules, especially the proximal tubules and interstitium, foreign body granulomas, cystic dilation of the renal tubules, and the formation of many fibrotic lesions. No abnormal changes were observed in the renal tissue of the control group.