动物造模,药效评价,急性肾衰竭 z-bio 2024-07-08 485

　　【 Modeling mechanism 】 Mercury ions are reabsorbed by renal tubular epithelial cells after filtration by the glomerulus, and accumulate inside the cells. They bind with cell membranes and intracellular thiol and disulfide groups, affecting cell enzyme activity, damaging the function and structure of cells and cell membranes, causing loss of cellular respiratory function, degeneration and necrosis, and partial detachment into the lumen, blocking the renal tubules and obstructing the passage of urine. Damaged renal tubules have increased permeability, causing the original urine to leak out and return to the renal vessels, resulting in oliguria and anuria. Primary urine leaks into the renal interstitium, causing interstitial edema and compressing renal tubules. Mercury chloride poisoning can also cause redistribution of renal blood flow, renal cortical ischemia, renal medullary congestion, and reduced renal tubular filtration, which is also one of the mechanisms leading to acute renal failure.

　　【 Modeling Method 】 Rabbits weighing over 2kg, both male and female. Mercury chloride is prepared with physiological saline or distilled water to an appropriate concentration and administered intravenously at a rate of 2.5mg/kg body weight. Measure the levels of urea nitrogen and Cr in blood and urine for the first 3 days of the experiment, and take the average value as the self control. Alternatively, intramuscular injection can be used to inject 10ml/kg body weight of 0.1% mercuric chloride solution into the hind limb muscles of rabbits for two consecutive days.

　　Model testing: ① Physiological and biochemical indicators: Cr and BUN levels rapidly increase after poisoning. After 24 hours, the Cr clearance rate significantly decreased, and the total excretion of Cr and BUN significantly decreased Urinary routine examination: Within 3-5 days after poisoning, there is obvious oliguria, followed by polyuria. Protein appears in urine, with various types of tubules Pathological examination: Significant enlargement of the kidney, increased weight (increased renal index), cortical ischemia, medullary congestion, and microscopic degeneration and necrosis of renal tubules.

　　【 Model Features 】 The filtration rate of the rabbit glomerulus decreases, causing degeneration and necrosis of renal tubular epithelial cells, renal vascular contraction, decreased renal blood flow, decreased renal perfusion pressure, impaired renal tubular secretion function, and renal tubular epithelial cell reabsorption dysfunction.

　　Model evaluation and application: This method is simple and feasible, and the lesion is relatively stable. The same applies to mice and rats, with a one-time administration of 0.1% mercuric chloride at a dose of 1.0-2.0mg/kg intravenously and 2-15mg/kg subcutaneously or intraperitoneally. For example, if selecting a dog, prepare a ureteral fistula for the dog before the experiment, and inject 2% mercuric chloride into the muscle, subcutaneous or abdominal cavity once at a dose of 20mg/kg body weight.