小鼠慢性肾功能不全模型 z-bo 2021-11-06 288

　　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 dosage 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. Detecting plasma creatinine and 24h urine protein excretion to evaluate mouse renal function; PAS staining to observe renal pathological changes; immunohistochemistry to detect kidney injury molecule 1 (KIM-1) and urine to detect N-acetyl-β-D amino group Glucosidase (NAG) level to assess 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, as the concentration of cisplatin injected increases, the kidney damage in mice is more obvious, and the 10mg/kg cisplatin high-dose group is 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 of renal tubular epithelial cells and vacuoles Significant pathological changes such as degeneration, renal tissue KIM-1 expression increased significantly (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 the renal tubule-interstitial fibrosis occurred.

　　 Conclusion: Repeated injections 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 studying the transformation mechanism of AKI to CKD.