动物造模,慢性肾功能不全模型 z-bio 2022-11-04 250

　　Objective: To establish a C57BL/6 mouse model of chronic kidney disease, explore the changes of tubule injury index and interstitial fibrosis degree with cisplatin modeling dose, and provide animal experimental basis for studying the progress from AKI to CKD.

　　Methods: Twenty four eight week old male C57BL/6 mice were randomly divided into control group and low, medium and high dose cisplatin model groups. The mice in the model group were intraperitoneally injected with 5, 7, and 10 mg/kg cisplatin once a week for 4 consecutive weeks. After the mice were killed, the specimens were taken for relevant tests. The renal function of mice was evaluated by measuring the plasma creatinine and 24-hour urinary protein excretion; PAS staining was used to observe the pathological changes of kidney; Immunohistochemical detection of KIM-1 and urine detection of N-acetyl- β- D-glucosaminidase (NAG) level was used to evaluate renal tubular injury; Immunohistochemistry was used to detect CD3 positive T cells and immunofluorescence was used to detect the infiltration of F4/80 positive macrophages; Detection of Collagen I and Collagen I by Sirius Red Staining and Immunohistochemistry α- Smooth muscle actin（ α- SMA) expression to evaluate renal fibrosis.

　　Results: Compared with the normal control group, with the increase of the concentration of cisplatin injected, the kidney damage of mice was more obvious, especially in the high-dose group of 10 mg/kg cisplatin. Compared with the control group, the renal function of mice in the high-dose cisplatin group decreased, which showed that the plasma creatinine concentration and 24h urinary protein excretion increased significantly (P<0.05 and P<0.001); The pathological changes such as necrosis and vacuolar degeneration of renal tubular epithelial cells were significant, the expression of KIM-1 in renal tissue was significantly increased (P; The number of infiltrating CD3 positive T cells and F4/80 positive macrophages in renal tissue increased; The number of Sirius red staining positive collagen fiber areas in renal tissue was significantly increased (P<0.001) α- The expression of SMA also increased significantly (P.

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