Abstract
Objective Different methods for the establishment of rat models of focal segmental glomerular sclerosis (FSGS) nephropathy were compared to identify the model that best simulated the human disease to provide a foundation for experimental studies of this disease.
Methods Forty-eight Sprague-Dawley rats were randomly assigned to eight groups (A‒H). Of these, group A, the control, received a single tail-vein injection of saline only. The rats in groups B, C, and D were injected with 5, 6, and 7 mg·kg-1 of adriamycin, respectively. Groups A‒D were assessed after three weeks. Groups E, F, and G received two doses of adriamycin, a first dose of 4 mg·kg-1 and second doses of 2, 3, and 4 mg·kg-1, respectively, at intervals of 14 days and were assessed after one week. The left kidneys in group H rats were surgically removed, and adriamycin (3 mg·kg-1) was injected into the tail vein on days 7 and 14 after surgery, with assessment one week later. The levels of 24 h urinary protein, serum creatinine (SCr), urea nitrogen (BUN), serum albumin (ALB), and serum total protein (TP) were measured, and pathological changes in the kidney were examined using HE, PAS, and Masson staining. The ultrastructural changes in the kidney were evaluated by transmission electron microscopy.
Results The biochemical indices showed that compared with group A, the 24 h urinary protein levels in groups B, C, and D were significantly increased at the end of the third week (P<0.05), while levels in groups F and H were significantly increased from the end of the sixth week (P<0.05). The SCr levels in groups G and H were significantly increased (P<0.05), as were BUN levels in groups C and D (P<0.05), while ALB was significantly reduced (P<0.05) in groups C, D, E, F,H, with the most marked reduction in group D. The serum TP contents in groups D, E, F, G, and H were significantly lower (P<0.05), especially in group H. Histological analysis of glomerular, tubular, and renal interstitial lesions showed a higher degree of renal lesions in the single-injection groups than in the double-injection or surgically-treated groups, and the degree of residual renal lesions in group H (surgical group) rats was comparable to that of group F. Electron microscopy showed that renal podocyte damage was greater in the single-injection groups, with a similar level of damage seen in groups H and F.
Conclusion Considering various factors such as survival and mortality, the overall renal damage in rats in Groups F and H (surgical group) were essentially the same, and they were more typical of human FSGS. Therefore, these two modeling methods can be widely used as a model to induce typical FSGS rat nephropathy, and can provide references for the study of FSGS nephropathy.