【Animal Modeling - Pharmacological Evaluation】 - Rat Acute Renal Failure Model

  1. Modeling material animals: Male SD rats weighing 180-250g; Medication: 50% glycerol.

  2. Modeling method: All animals were weighed before the experiment and deprived of water for 24 hours. Those who lost more than 10% of their body weight entered the experiment and were randomly divided into two groups: the model group [acute renal failure (ARF) group]: 50% glycerol was injected into the bilateral hind leg muscles at a dose of 10ml/kg; the control group: physiological saline was injected into the bilateral hind leg muscles at a dose of 10ml/kg. Then drink water freely and feed with standard feed.

  3. Modeling principle: After intramuscular injection of glycerol, the renal blood flow in rats decreases, the endothelial cells of renal tubules swell, increasing renal vascular resistance, segmental necrosis of blood vessels, outer membrane fibrosis, loss of vascular self-regulation function, leading to a decrease in glomerular filtration rate. In addition, fibrin deposition around the glomerulus and renal tubules, intravascular blood stasis, thrombus formation, and poor blood flow lead to a decrease in glomerular filtration rate and tubular necrosis.

  4. After modeling, the control group rats showed shiny body hair, quick reflexes, and normal diet. After injection, the ARF group experienced significant local pain, delayed response, dull body hair, edema in the injection area, and reduced dietary intake. After 1 hour, gross hematuria appeared, and the urine volume decreased within 24 hours after modeling, then gradually increased, and the urine color was a soy sauce color.

  5. After modeling, the biochemical and pathological changes showed that compared with the control group, the blood urea ni nitrogen (BUN) in the ARF group significantly increased from 6 hours [(16.19 ± 2.09) mmol/L] and reached its peak at 72 hours [(79.06 ± 14.40) mmol/L]. The changes in creatinine (Cr) occur earlier than BUN, increasing at 1 hour [(62.70 ± 7.07) mol/L], reaching a peak at 48 hours [(296.20 ± 57.10) mol/L], and gradually decreasing until 120 hours before returning to normal. BUN and Cr showed significant differences compared to the control group from 6 to 120 hours and 1 to 120 hours, respectively.

  Visual observation: The appearance of the kidneys in the control group rats is not swollen, and the color is normal; The kidneys in the ARF group became larger, edematous, and had a darker purple black color, with bleeding spots on the surface, and the medulla was more congested than the cortex.

  Under the microscope observation: the control group was basically normal; In the early stage of ARF group, the renal tubular epithelial cells showed cloudy swelling and watery degeneration, and the glomeruli were congested and swollen, with a small amount of fibrin deposition in the glomeruli; After 24 hours, the epithelial cells of the proximal tubules disintegrated and necrotic; A large amount of protein is formed in the distal tubules, and necrotic and shed cells form cell casts, with loose tissue structure and urine extravasation; After 72 hours, the tubular shape in the small lumen gradually dissolved and disappeared, and regenerated epithelial cells at the site of intermittent damage to the renal tubular epithelium began to be visible.

  6. Precautions: Some rats may die from severe kidney damage after intramuscular injection of glycerol. Rats with significant weight loss and severe dehydration after 24 hours of water deprivation showed better results as experimental animals.