动物造模,慢性肾功能不全模型 z-bio 2021-07-03 364

　　OBJECTIVE: To establish a C57BL/6 mouse model of chronic kidney disease (CKD) to study the effects of cisplatin doses from AKI to CKD on renal tubular injury index and interstitial fibrosis.

　　Method: Twenty-four 8-week-old male C57BL/6 mice were randomly divided into control group and low-dose, medium-dose and high-dose cisplatin model groups. The model was established by intraperitoneal injection of 5, 7 and 10 mg/kg of cisplatin into the intraperitoneal model group once a week for 4 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.

　　Result: Compared with the normal control group, the increase in the concentration of cisplatin injection caused more obvious kidney damage in mice, and the highest dose of 10 mg/kg cisplatin group was the most obvious. Compared with the control group, the renal function of the mice in the high-dose cisplatin group decreased, which can be demonstrated by the significant increase in plasma creatinine concentration and 24-hour urine protein excretion (P\u003c0.05 and P\u003c0.001). ); renal tubular epithelial necrosis and vacuoles. Significant 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 significantly increased Sirius For collagen fibers with positive red staining (P\u003c0.001), the expression of collagen I and α-SMA increased significantly (P\u003c0.01), and renal tubulointerstitial fiber I was diseased.

　　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 into CKD.