Establishment of focal segmental glomerulosclerosis models induced by nephrectomy combined with adriamycin in rabbits / 中国组织工程研究

ABSTRACT

BACKGROUND: Rat models induced by unilateral nephrectomy combined with adriamycin are widely used in screening anti-drugs of glomerular sclerosis. However, few reports concerning this method on inducing rabbit model of glomerular sclerosisOBJECTIVE: To establish a rabbit model of glomerular sclerosis, and to observe the renal function and histopathological changes during model preparation. DESIGN, TIME AND SETTING: Randomized controlled animal experiment was performed in Laboratory Animal Center of Kunming General Hospital of Chengdu Military Region between December 2008 and May 2009. MATERIALS Twenty-five Japanese big-ear rabbits, weighing 1.75-2.25 kg, half males and half females, were selected to establish glomerular sclerosis models, and randomly divided into normal (n=10) and model (n=15) groups. METHODS: The left kidney of rabbits in the model group was removed under anesthetized with 30g/L saline solution of sodium pentobarbital (1 mL/kg). Rabbits in the normal group underwent a similar surgical procedure without kidney removing. At 1 week after operation, 5 mg/kg adriamycin was injected into rabbits in the model group, 3 mg/kg adriamycin was reinjected 2 weeks later. Same volume of physiological saline was injected in the normal group. MAIN OUTCOME MEASURES: The renal blood biochemical indexes were detected prior to and at weeks 4, 6, and 8 after model preparation. One nephridial tissue was harvested from each group to undergo pathological observation at week 8 after the second medication. RESULTS: ①Kidney in the normal group presented slightly white, slightly tough texture with smooth surface. ②Pathological features of focal segmental glomerulosclerosis was showed in the model group under a light microscope, presented as extracellular matrix hyperplasia, mesangial region expansion, renal glomerular capillary wall ball mix adhesion, tubule degeneration, or even interstitial fibrosis, as well as interstitial infiltration of inflammatory cells. ③Compared to the normal group, the total protein and albumin was and decreased, triglyceride, total cholesterol, low density lipoprotein cholesterol, urea nitrogen, and creatinine were significantly increased in the model group. The urine protein content of rabbits in the model group was obviously increased at 4 weeks, gradually reached a platform after 8 weeks, which still greater than that of the normal group. ④SPECT showed that the glomerular filtration rate of the model group was notably decreased (33 mL/min) than the normal group (92.6 mL/min).CONCLUSION: The unilateral nephrectomy combined with adriamycin in rabbits results in the formation of glomerular sclerosis, renal function and 24 h urinary protein is more visible in the phase change.