New rat passive membranous nephropathy model induced by rabbit anti-human podocyte-protein antibody / 中华肾脏病杂志

ABSTRACT

Objective To investigate the clinical and renal pathological features in the new rat model induced by anti-human podocyte-protein antibody. Methods The rat model was induced by once intravenous injection of rabbit anti-human podocyte-protein antiserum which was prepared at first. Male Sprague-Dawley rats (n=36) were randomly divided into six groups (6rats in each group) control group (CG), the time points of day 7 group (D7), day 14 group (D14),day 21 group (D21) and day 28 (D28) group after antiserum injection, and day 28 group after the normal rabbit serum injection (NRG). The level of 24 hour proteinuria, the clearance of creatinine,albumin, blood urea nitrogen, triglyceride, cholesterol and serum creatinine were measured. The renal morphology was detected under the light microscope, immunofluorescence microscope, and electron microscope. Results 24-hour proteinuria (mg) was gradually increased, and the level of proteinuria in D28 (48.56±13.80) was significantly higher than that in CG (5.34±2.77, P＜0.01)and NRG (11.32±4.90, P＜0.01). The clearance of creatinine (ml/min) and serum creatinine (μmol/L) in D28 (0.90±0.47, 33.48±9.94) were significantly different from CG (1.68±0.54, P＜0.05;26.03±2.67, P＜0.05), but showed no difference with NRG (1.34±0.87, P＞0.05; 27.40±4.73, P＞0.05). The level of albumin (g/L) was lower in D7, D14, D21, D28 (28.20±0.87, 27.80±1.97,27.42±1.66, 27.77±1.95) than CG (29.98±0.76, P＜0.05). But there was no difference in the level of albumin among the groups after antiserum injection and NRG (28.68±1.18, P＞0.05). The level of blood urea nitrogen, triglyceride, cholesterol showed no difference among the groups (P＞0.05). The renal morphology showed no obvious changes between CG and NRG. Among the groups after antiserum injection, the renal pathological changes under the light microscope were some spikes formation in D28. Immunostained for rabbit IgG in rat glomeruli progressively decreased over the 28 days, while rat IgG progressively increased. The renal section deposition for rat complement 3 reached a maximum at day 21 then decreased afterward. Under the electron microscope, there were immune complexes and foot process fusion at day 14. Conclusions The new rat model induced by anti-human podocyte-protein antibody showing typically clinical and pathological changes of the membranous nephropathy is successfully established.