动物造模,慢性肾功能不全模型 z-bio 2022-09-20 449

　　OBJECTIVE: To construct a C57BL/6 mouse model of chronic kidney disease, and to explore the changes of its tubular injury indexes and interstitial fibrosis with the dose of cisplatin, so as to provide an animal experimental basis for studying the progression from AKI to CKD.

　　METHODS: Twenty-four 8-week-old male C57BL/6 mice were randomly and equally divided into control group and low-, medium- and high-dose cisplatin model groups. Mice in the model group were given intraperitoneal injection of 5, 7, and 10 mg/kg of cisplatin, once a week, for 4 consecutive weeks to establish a model. After the mice were sacrificed, specimens were collected for relevant testing. Plasma creatinine and 24h urinary protein excretion were detected to evaluate mouse renal function; PAS staining was used to observe renal pathological changes; immunohistochemical detection of renal injury molecule 1 (KIM-1) and urine detection of N-acetyl-β-D amino Glucosidase (NAG) level to evaluate renal tubular damage; immunohistochemistry to detect renal CD3 positive T cells and immunofluorescence to detect F4/80 positive macrophage infiltration; Sirius red staining and immunohistochemistry 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 of the injection concentration of cisplatin, the kidney injury of the mice was more obvious, and the 10 mg/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, and the plasma creatinine concentration and 24-hour urinary protein excretion were significantly increased (P<0.05 and P<0.001); renal tubular epithelial cell necrosis, vacuoles Degeneration and other pathological changes were significant, the expression of KIM-1 in renal tissue was significantly increased (P<0.05), and the level of urinary NAG was increased; CD3-positive T cells and F4/80-positive macrophages infiltrated in renal tissue increased; renal tissue Sirius red staining The positive collagen fiber area was significantly increased (P<0.001), the expression of collagen I and α-SMA was also significantly increased (P<0.01), and the renal tubule-interstitial fibrosis occurred.

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