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The Experimental Study Of Pristane-Produced MurineLupus Model

Posted on:2005-06-23Degree:MasterType:Thesis
Country:ChinaCandidate:G M CuiFull Text:PDF
GTID:2144360155973250Subject:Internal Medicine
Abstract/Summary:
One of methods to study the pathogenesis of systemic lupus erythematosus (SLE) is using animal models, which were mainly divided into genetic and chemicals-produced murine lupus models. The latter was usually used to study the role of environmental factors in the pathogenesis of SLE. Pristane-primed mouse model was more similar to human SLE than others in chemicals-produced lupus animal models, including drugs. This study established SLE animal model in BALB/c mice successfully based on references.Objective To establish a mouse model of SLE and to discuss the role of environmental factors in the pathogenesis of lupus.Methods Thirty 10-week-old female BALB/c mice, special pathogen free(SPF), were divided into model and control groups. 24 model mice received a single intraperitoneal injection of 0.5ml of pristane, while 6 control mice received a single i.p. injection of 0.5ml of 0.9%NS. Sera were obtained before injection and at 2 weeks, monthly thereafter to detect ANA and anti-dsDNA antibody. Urine samples were tested monthly for protein concentration by using Albustix reagent strips. 7-8 months after injection, all mice were bled to death. Kidneys were excised from pristane-primed andcontrol mice to observe the histopathologic evidence of glomerulonephritis. SPSS was used to finish the statistical analysis of the detective value from two groups.Results In model mice, ANA appeared in sera as early as 3 months, but anti-dsDNA antibody was appeared at 4 months. 7 months after pristane injection, 87.5% sera were ANA positive and 47.8% sera were anti-dsDNA antibody positive. The protein concentration of urine in most mice was above 30mg/dl. Light microscopy of kidney sections from 10 model mice revealed the glomeruli were larger than those of controls, indicating proliferative glomerular lesions. Proliferation was also seen in tubular epithelial cells and there was proteinosis in the cavity of tubular. Cryostat sections of kidney were stained with 1:50 dilution of FITC conjugated rabbit anti-mouse antibody. Note predominant mesangiocapillary distrbution of immue-complex deposits. In control mice,7 months after injection of 0.9%NS, one of six mice was ANA positive, one of six was anti-dsDNA antibody positive while ANA negative. The protein concentration of urine was equal or below 30mg/dl. The histopathology and direct immunofluorescence staining showed no evidence of lesions of kidneys. There was significant statistical difference in incidence and titer of ANA between two groups(P<0.01). There was no statistical difference in incidence and titer of anti-dsDNA antibody between two groups(P>0.05). The incidence and semi-quantity of protein concentration of urine had statistical difference (P<0.05). Anti-dsDNA antibody was associated with proteinuria (r=0.538,P=0.003).Conclusion The SLE animal model can be successfully established in female BALB/c mice with a single i.p. injection of 0.5ml of pristane. The environmental factors play an important role in the pathogenesis of SLE.
Keywords/Search Tags:systemic lupus of erythematosus, auotoantibodies, lupus nephritis, murine,inbred BALB/c, animal model.
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