【Animal modeling】-animal model of renal tubulointerstitial fibrosis

  [Modeling mechanism] Renal vein ligation can lead to renal ischemia, renal tubular injury, ischemic atrophy and tubular loss, renal interstitial hyperplasia and tubular interstitial fibrosis (TIF) [Modeling method: weight 200- Wistar rats were anesthetized with 250 grams of 8.5% by weight chloral hydrate (0.1 ml/kg), and the curtains were disinfected regularly after local shaved. Then, the skin was cut into the abdominal cavity along the midline of the abdomen, and the renal vein was ligated with 4-0 sutures on the 5th, 10th, 15th, 20th and 25th days after the operation. The rats were sacrificed on the kidney and placed in a metabolic cage before sacrifice. Keep urine for 24 hours to test regular urine. Collect femoral artery blood and detect Cr content. Using H&E, PAS, PASM and Masson, the kidneys on both sides were fixed with 10% neutral formaldehyde solution, dehydrated regularly, embedded in paraffin, and fixed to a thickness of 4μm.

  1. The lesion is typical and stable, and the lesion on the surgical side is very similar to human TIF. Through dynamic observation, the initial histological change of the lesion is renal tubular epithelium. Degeneration and atrophy, interstitial congestion, mainly edema, monocyte infiltration and collagen proliferation in the interstitium; in the middle and late stages, renal tubules atrophy and disappear, the arterial wall renal interstitial fibroblasts thicken, collagen deposition, and collagen Hyperplasia. Overall. During the course of the disease, glomerular ischemic changes can be seen.

  2. The cycle is short and the operation method is simple. It only separates and ligates the renal vein. The operation process only takes 20 minutes. One kidney is operated on, and the other kidney is not affected. The damage has a slight impact on the life of the animal. The experimental period is short. The ideal tubular interstitial fibrosis formed on the 10th day.

  [Model evaluation and application] Renal vein ligation is a method that is simple, has a high success rate, and has stable disease. The animal model of renal tubulointerstitial fibrosis is very similar to human diseases and overcomes the shortcomings of other models. Common methods include unilateral ureteral ligation and renal insufficiency, such as complete resection, immune intervention, gentamicin renal tubular injury, adenine fibrosis, radiation injury and infection. Yes, especially for nephritis caused by drugs, such as cyclosporine and doxanol than xin nephritis, etc. The methods are simple to operate and have a high success rate, but they are expensive, the experimental period is long and the interstitial changes are small. Nephrectomy can cause TIF lesions, but the procedure is complicated and more harmful to animals. The immune-mediated nephritis model can obtain TIF lesions by prolonging the pathogenic cycle, but the results obtained are unstable. The lesions in the adenine-induced fibrosis model are stable, but should be given daily according to the animal's body weight. The operation is very troublesome. The cycle will also be longer. Gentamicin renal tubular injury models are mainly acute necrosis and tubular epithelial regeneration. Interstitial fibrosis is still unclear. The unilateral ureteral ligation model damages the kidney tissue by retaining and compressing urine, causing interstitial fibrosis. Usually controlled for about 15 days, but as time goes on, the kidney parenchyma will be compressed. It became too thin, and interstitial fibrosis was not obvious by day 15.