动物造模,慢性肾功能不全 z-bio 2021-12-30 1383

　　OBJECTIVE: To construct a C57BL/6 mouse model of chronic kidney disease, to explore the changes in tubule damage indexes and interstitial fibrosis with the dose of cisplatin, and to provide animal experimental evidence for the study of the progression from AKI to CKD.

　　Method: Twenty-four 8-week-old male C57BL/6 mice were randomly divided into a control group and a low, medium, and high dose cisplatin model group. Mice in the model group were injected intraperitoneally with 5, 7, 10 mg/kg cisplatin, once a week, for 4 consecutive weeks to construct a model. After the mice were sacrificed, specimens were collected for related testing. Detection of plasma creatinine and 24h urine protein excretion to assess renal function in 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 amino group Glucosidase (NAG) level to evaluate renal tubular damage; immunohistochemical method to detect kidney CD3 positive T cells and immunofluorescence method to detect F4/80 positive macrophage infiltration; Sirius red staining, immunohistochemical method to detect collagen I And α-smooth muscle actin (α-SMA) expression to assess renal fibrosis.

　　Results: Compared with the normal control group, with the increase in the concentration of cisplatin injection, the kidney damage in mice was more obvious, and the 10mg/kg cisplatin high-dose group was the most significant. Compared with the control group, the renal function of the mice in the high-dose cisplatin group decreased, manifested by significantly increased plasma creatinine concentration and 24h urine protein excretion (P＜0.05 and P＜0.001); necrosis and vacuoles of renal tubular epithelial cells Significant pathological changes such as degeneration, renal tissue KIM-1 expression significantly increased (P<0.05), urine NAG level increased; kidney tissue infiltrated CD3 positive T cells and F4/80 positive macrophages increased; kidney tissue Sirius red staining The area of positive collagen fibers increased significantly (P<0.001), the expression of collagen I and α-SMA also increased significantly (P<0.01), and renal tubule-interstitial fibrosis occurred.

　　Conclusion: Repeated injection of 10 mg/kg cisplatin for 4 weeks can induce a model of chronic renal insufficiency in mice, which can provide a new experimental model for the study of the transformation mechanism of AKI to CKD.