Protective effect of dexamethasone implant on nephrotoxicity of adriamycin in rats
10.12092/j.issn.1009-2501.2020.06.002
- VernacularTitle: 阿霉素对大鼠的肾脏毒性及地塞米松植入剂的保护作用
- Author:
Cheng ZHANG
1
Author Information
1. Department of Pharmacology, Anhui Medical University
- Publication Type:Journal Article
- Keywords:
Dexamethasone implants;
Podocyte;
Renal capsule implantation;
Slit diaphragm
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2020;25(6):610-617
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To study the establishment of adriamycin nephropathy rat model and the protective effects and mechanisms of dexamethasone implants (DEXI) through renal capsule implantation. METHODS: The adriamycin-induced nephropathy model was built by injecting Adriamycin (4 mg/kg) and Adriamycin (3.5 mg/kg) was injected again after week into tail-vein in SD rats. Renal capsule puncture was performed in model group. The excipient control group injected intra-renal capsule with drug-free excipient (1.4 mg/kg). The experimental group (2.8, 1.4, 0.7 mg/kg) was given by intrarenal capsule injection and positive drug group (0.1 mg/kg, qd × 8 w) was made by intragastric administration. The rat weight, kidney function and blood biochemical were observed and detected during the experiment. After the experiment, rat kidneys were stained with periodic acid-schiff to observe the morphological changes of mesangial and basement and sirius red to observe the renal tissue collagen fibers, expression of podocin and CD2AP were detected by immunohistochemistry. RESULTS: The blood protein content of adriamycin rats decreased, total blood cholesterol, uric acid, blood creatinine and urea nitrogen increased (P<0.05 or P<0.01), mesangium and fibers increased. The expression of Podocin protein in kidney tissue decreased and the expression of CD2AP protein increased (P<0.05 or P<0.01). DEXI increased the weight and blood protein levels of adriamycin rats, reduced blood lipids and blood uric acid levels (P<0.05 or P<0.01), improved renal function and tissue damage, and regulated the abnormal expression and distribution of Podocin and CD2AP proteins (P<0.05 or P<0.01). CONCLUSION: These results suggest that injecting adriamycin into the tail vein can establish a stable kidney disease model. DEXI renal capsule implantation can improve adriamycin nephropathy injury, and its mechanism may be related to restoration the expression and distribution of Podocin and CD2AP proteins on podocyte slit diaphragm.
