Rabbit Models Of Systemic Lupus Erythematosus Induced With Hepatic Cytoplasmic Protein And Nucleoprotein

Objective:To investigate the rabbit models of Systemic lupus erythematosus (SLE), which could complement knowledge derived from the more frequently used mouse models of this disease, moreover, it may also provide additional information about the etiology of SLE and serve as a model for assessing new treatment options.Methods:50 female New Zealand rabbits aged 1 year were divided into five groups, with ten rabbits each group. The cytoplasmic protein and nucleoprotein were extracted from allogeneic liver, that were diluted in PBS. The rabbits were immunized with 500μg of protein in each rabbit at week 0,1, 2,4,6,8,10,12. The rabbits in model group 1 were immunized by hypodermic injection of nucleoprotein; The rabbits in model group 2 were immunized by hypodermic injection of cytoplasmic protein; The rabbits in model group 3 were immunized by intravenous injection of cytoplasmic protein; The rabbits in control group 1 were made by hypodermic injection of PBS; The rabbits in control group 2 were made by intravenous injection of PBS. The primary immunizations of model group 1,2 and control group 1 were performed with FCA.The rabbits were observed for 18 weeks, were collected blood and urine of 24 hours every other week. The observed items include Scr, BUN, TP, ALB, ALT, AST and 24h urine protein, the ANA, anti-dsDNA and anti-Sm antibody were measured by ELISA test. Skin sections from the rabbits were stained with hematoxylin and eosin(HE), immunohistochemistry. Kidney sections from the rabbits were stained with HE, Masson, immunohistochemistry, and that results were evaluated semi-quantificationally.Results:1. Blood biochemical parameters:the serum creatinine of model group 1,2 both were significantly higher than control group 1 at week 12,16,18(P<0.05); The serum creatinine of model group 3 was significantly higher than control group 2 at week 12,14,16,18 (P＜.05); Albumin of three model groups was decreased, but that were lower than control groups at week 16,18. BUN, TP, AST, ALT of model groups were not increased up during 18 weeks.2. Auto-antibodies:anti-Sm antibody and anti-dsDNA antibody responses were seen in 86.7% of model groups immuzed (9 of 10 rabbits in model group 1, 9 of 10 rabbits in model group 2,8 of 10 rabbits in model group 3). Only one rabbit in model groups was observed increase of ANA. The anti-Sm antibody and anti-dsDNA antibody of model group 1,2,3 were significantly higher than control groups (P<0.01), but no statistically significant differences amang control groupl, control group 2, and model groups preimmuzed (P>0.05). To compare these tree model groups, the anti-Sm antibody of the model group 1 was higher than model group 2 at week 4,6,8 (P<0.05), and the anti-dsDNA antibody of this group was higher than model group 2,3 at week 4, 6,10,16,18 (P<0.05). No statistically significant differences amang model group 2 and model group 3 (P>0.05).3. The 24h urine protein:the 24h urine protein of 43.3% rabbits in model groups was more than twice the reference value (4 of 10 rabbits in model group 1,4 of 10 rabbits in model group 2,5 of 10 rabbits in model group 3). The 24h urine protein of model group 3 were significantly higher than control group 2 (P<0.01); that dosage of model groups was rise up with time. No statistically significant differences amang control groupl, control group 2, and model groups preimmuzed (P>0.05).4. The pathological changes of kidney:The pathological changes of kidneys were observed in 20 rabbits in model groups, with 67% of all model groups (6 of 10 rabbits in model group 1,6 of 10 rabbits in model group 2,8 of 10 rabbits in model group 3), and none pathological changes of kidney in control groups. The pathological changes of glomerulus, renal tubules and renal interstitial were observed among these three model groups, that had significant difference from the control groups (P＜0.01). The mesangial proliferative glomerulonephritis was observed in glomerulus stained with HE in these three model groups. Glomerulosclerosis was seen in model group 3. Immunohistochemistry showed deposits of IgG along the mesangial area in model goups. No deposits of IgG along the mesangial area in control groups.5. Skin lesions:Skin lesions were observed in 22 rabbits in model groups, with 73% of all model groups (7 of 10 rabbits in model group 1,7 of 10 rabbits in model group 2,8 of 10 rabbits in model group 3). The lesions were mainly included erythema, scale and molt, became more serious as amaranth indurated erythematous patch and toe ulcer. Pathology of skin showed that liquefaction of basal cells in rabbit model groups. No lesion was observed in control groups.Conclusion:The rabbit SLE model was able to be established with immunized by allogeneic liver cytoplasmic protein and nucleoprotein, the high level of autoantibodies observed in the rabbit SLE model induced with nucleoprotein was higher than which with cytoplasmic protein, and more serious cutaneous lesions in rabbits induced by cytoplasmic protein. In comparison with two routes of administration of cytoplasmic protein, more serious kidney problems were observed in the rabbits induced intravenously, and more serious cutaneous lesions in rabbits induced subcutaneously.