[Animal Modeling]-Establishment of a mouse model of chronic renal insufficiency induced by repeated injection of cisplatin

  Objective: To establish a C57BL/6 mouse model of chronic kidney disease, to study the changes in renal tubular injury index and interstitial fibrosis caused by cisplatin dose, and to conduct animal experiments to study the progress of AKI and CKD to provide relevant evidence.

  Method: 24 male C57BL/6 mice aged 8 weeks were randomly divided into a control group and a low, medium, and high dose cisplatin model group. The model was constructed by intraperitoneal injection of 5, 7, and 10 mg/kg cisplatin into the mouse model group once a week for 4 consecutive weeks. After the mice were sacrificed, specimens were collected for related tests. Detection of plasma creatinine and 24-hour urine protein excretion to evaluate the renal function of mice; PAS staining to observe the pathological changes of the kidney; immunohistochemical detection of kidney injury molecule 1 (KIM-1) and urine detection of N-acetyl-β-D Used to assess the level of glucosaminidase (NAG) for renal tubule damage; immunohistochemical method for the detection of renal CD3 positive T cells and F4/80 positive macrophages infiltration; Sirius red staining for detection of immunofluorescence; The immunohistochemical method used to detect collagen I and α-smooth muscle actin (α-SMA) expression is used to assess renal fibrosis.

  Results: Compared with the normal control group, with the increase of the cisplatin injection concentration, the kidney damage to the mice became more obvious, and the high-dose 10 mg/kg cisplatin group was the most important. Compared with the control group, the renal function of the mice in the high-dose cisplatin group decreased, and the plasma creatinine concentration and 24-hour urine protein excretion significantly increased (P\u003c0.05 and P\u003c0.001). Renal urination and renal tubular epithelium were visible. Necrosis and vacuoles. Major pathological changes, such as cell degeneration, renal tissue KIM-1 expression significantly increased (P\u003c0.05), urine NAG level increased, renal tissue infiltration of CD3 positive T cells and F4/80 positive macrophages increased Silius red staining Positive collagen fibers (P\u003c0.001), collagen I and α-SMA expression increased significantly (P\u003c0.01), and tubular interstitial fibrosis has occurred.

  Conclusion: Repeated injection of 10 mg/kg cisplatin for 4 weeks can induce a mouse model of chronic renal failure, which provides a new experimental model for studying the mechanism of AKI transforming into CKD.