Animal model of gentamicin nephropathy

Summary

Gentamicin is an aminoglycoside antibiotic widely used in the treatment of gram-negative bacterial infections. However, the nephrotoxicity of gentamicin (which can lead to acute tubular necrosis or acute renal failure) has led to limitations in its use. The incidence of gentamicin nephrotoxicity is 10% to 20%. The mechanism of gentamicin nephropathy is still unclear, therefore, the establishment of animal models of gentamicin nephropathy is of great theoretical and practical significance for just clarifying the mechanism of the injury and discussing the prevention and treatment measures.

Principle

Depending on the experimental method, the corresponding principles are different:

Basic principles of the animal model of gentamicin nephropathy:

Studies have shown that endoplasmic reticulum stress, apoptosis, lysosomal enzyme release, impaired cellular energy status, oxidative stress, and CaSR (a member of the cell membrane C-protein-coupled receptor family) may be closely related to the development of gentamicin nephrotoxicity. The pathological features are mainly characterized by the effects of gentamicin on the renal tubules, including loss of the brush border of epithelial cells, tubular necrosis, tubular epithelial edema and epithelial cell detachment.

Appliance

The commonly used application areas of gentamicin nephropathy animal model are as follows: it can be applied to gentamicin kidney injury animal model to elucidate the mechanism of its occurrence leading to acute kidney injury, to explore the effective interventional therapeutic measures, and to explore the rational method of drug administration.

Operation method

Animal model of gentamicin nephropathy

Principle

Studies have shown that endoplasmic reticulum stress, apoptosis, lysosomal enzyme release, impaired cellular energy status, oxidative stress, and CaSR (a member of the cell membrane C-protein-coupled receptor family) may be closely associated with the development of gentamicin nephrotoxicity. The pathological features are mainly characterized by the effects of gentamicin on the renal tubules, including loss of the brush border of epithelial cells, tubular necrosis, tubular epithelial edema and epithelial cell detachment.

Materials and Instruments

Subjects:
① Rats.
Experimental reagents:
① 4% formaldehyde solution;
② Gentamicin sulfate.

Move

The basic process of the animal model of gentamicin nephropathy can be divided into the following steps:
A

. Modeling method of gentamicin nephrogenic rat model. Clean grade Wistar rats, weighing 250-350 g, were divided into experimental and control groups. In the experimental group, the rats were injected intraperitoneally with gentamicin sulfate at a dose of 80-100 mg/kg once a day for 7-10 consecutive days. The control group was injected with an equal amount of physiological sterile saline. Then, blood and 24-hour urine were collected respectively, and blood creatinine, blood urea hydrogen, blood potassium, blood sodium, urine creatinine, urine sodium and 24-hour urine protein were measured by automatic biochemical analyzer. The kidney specimens were fixed with 4% formaldehyde solution, embedded in paraffin, and then serially sectioned, routinely stained with HE and PAS, and the histopathological changes of the kidney were observed under a light microscope.

B. Modeling method of gentamicin nephrotoxicity in mini-pigs Male mini-pigs at 6 months of age, weighing 6-8 kg, were randomly divided into 2 groups. In the normal control group, 1 mL of saline was injected daily for 10 days. In the gentamicin group, gentamicin sulfate was injected intramuscularly at a dose of 80 mg/kg once a day for 10 consecutive days. At the end of the injection on the 10th day of the experiment, blood and urine specimens were taken for the determination of creatinine, urea nitrogen and other biochemical indexes; kidney specimens were fixed in 4% formaldehyde solution, and then stained and analyzed by HE, PAS and other staining analyses, and the pathological changes were examined under the light microscope.

Caveat

1. Gentamicin nephrotoxicity rat model. Compared with the control group, the blood creatinine and urea nitrogen of rats in the gentamicin model group were significantly elevated, and the blood potassium level was significantly elevated. Pathological manifestations: extensive necrosis of renal cortical tubules, detachment of tubular epithelium, vacuolization of tubular epithelium, tubular atrophy, interstitial coagulation and edema, degeneration or dilatation of proximal and distal renal tubules.

2. Small pig model of gentamicin nephrotoxicity. Blood urea nitrogen, creatinine and blood potassium were significantly elevated in the gentamicin model group compared with the normal control group. Pathological manifestations: In the model group, the renal tissues of minipigs showed extensive damage, mainly manifested by tubular necrosis, tubular epithelial edema and epithelial cell detachment, and the tubular lumen was filled with red granular necrotic material.

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