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Empirical Study of Neutralizing Monoclonal Antibodies of Anti-GBM Antibody Against Established Anti-GBM Glomerulonephritis in Rats

Author: NieZhiYong
Tutor: LiuZhangSuo
School: Zhengzhou University
Course: Internal Medicine
Keywords: anti-glomerular basement membrane glomerulonephritis monoclonal antibody rapidly progressive glomerulonephritis crescentic glomerulonephritis kidney
CLC: R692.3
Type: Master's thesis
Year: 2010
Downloads: 37
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Abstract


ObjectiveThe direct pathogenic factor of the anti-glomerular basement membrane glomerulonephritis is the formation of anti-GBM antibody, anti-GBM antibody combined withα3 (Ⅳ) NC1 specificity which is the target antigen of GBM, resulting in a large number of crescent formation. Immunofluorescence IgG-type anti-GBM antibodies along the GBM showed diffuse deposition of thin wire-like. Anti-GBM glomerulonephritis received extensive attention in recent years. So far, the potential pathogenic mechanism of anti-GBM glomerulonephritis has not been completely clear, and the therapeutic measures for anti-GBM glomerulonephritis are still poor. In theory, neutralizing monoclonal antibodies (MAbs) of anti-GBM antibody may inhibit the anti-GBM antibody combined withα3 (Ⅳ) NC1 of the target antigen, thus preventing disease progression.The purpose of this study is to inject neutralizing monoclonal antibodies into anti-GBM nephritis in rats, to observe a variety of biochemical markers and renal pathological changes, and to discuss the mechanism of action of Mabs.MethodsForty-five Wistar rats were equally divided into 5 groups, each group has 9 rats. (1)nephritis model group in which the rats received human anti-GBM antibody (1.5mL/100g) with an equal dose of Freund’s complete adjuvant (FCA) emulsion by injection method via the caudal vein.(2)normal control groupⅠwere injected with normal human serum (1.5mL/100g) instead of human anti-GBM antibody with the same dose of FCA emulsion. (3)control groupⅡwere injected with neutralizing monoclonal antibodies (MAbs) of anti-GBM antibody(1.5mL/100g) with an equal dose of FCA emulsion.(4)The intervention groupⅠwere injected with human anti-GBM antibody (1.5mL/100g) and an equal dose of FCA emulsion, the first seven days later were injected with neutralizing MAbs of anti-GBM antibody(1.5mL/100g).(5)The intervention groupⅡwere injected with human anti-GBM antibody (1.5mL/100g) and an equal dose of FCA emulsion,14 days later later were injected with neutralizing MAbs of anti-GBM antibody(1.5mL/100g).Bodyweight,24h urinary protein excretion, Blood urea nitrogen,Serum creatinine, renal light microscopy and immunofluorescence changes were measured at 7th day,14th day,21st day, respectively.Results①Compared with the nephritis model group, the 24h urinary protein excretion, BUN, Scr of rats in the intervention groupⅠwere decreased, the difference was not statistically significant (P>0.05);But more significantly increased than that in the normal control groupⅠand the control groupⅡ, with a significant difference on the 14th day(P<0.05).②Compared with the nephritis model group, the 24h urinary protein excretion, BUN, Scr of rats in the intervention groupⅠwas significantly decreased on the 21st day (P<0.05).③Compared with the normal control groupⅠ, renal glomerulus volume of rats in the intervention groupⅠwas increased, showing that cellular crescent formation, part of the glomerular cavity shrinkage; However, compared with the nephritis model group, cellular crescent of rats in the intervention groupⅠwas significantly decreased,and a small amount of protein cast of renal tubular was observed on the 14th day.④Compared with the normal control groupⅠand the control groupⅡ, the area of glomerular crescent in the nephritis model group, the intervention groupⅠand the intervention groupⅡwas significantly increased, with a significant difference on the 14th day(P<0.05);But the area of glomerular crescent in the intervention groupⅠwas slightly less than that in the nephritis model group, the difference was not statistically significant on the 14th day (P>0.05).⑤In the kidney tissue, compared with nephritis model group the fluorescence intensity in the intervention groupⅠwere significantly weaker on the 14th day and the first 21 day,and the intensity of staining was denoted as 1+;The above parameters were not significant changes inthe normal control groupⅠand control groupⅡ.⑥Compared with nephritis model group, the 24h urinary protein excretion, BUN, Scr of rats in the intervention groupⅡwere decreased, the difference was not statistically significant (P>0.05); But more significantly increased than that in the normal control groupⅠand the control groupⅡ, with a significant difference on the 21st day(P<0.05).⑦Compared with the normal control groupⅠand the control groupⅡ, the area of glomerular crescent in the nephritis model group, the intervention groupⅠand the intervention groupⅡwas significantly increased, with a significant difference on the 21st day(P<0.05);However,the area of glomerular crescent in the intervention groupⅠwas more significantly decreased than that in the nephritis model group, with a significant difference on the 21st day (P<0.05). The area of glomerular crescent in the intervention groupⅡwas slightly less than that in the nephritis model group, the difference was not statistically significant on the 21st day (P>0.05).⑧Kidney immunofluorescence intensity in the intervention groupⅡwere weaker than the nephritis model group on the 21st day, the results were 2+.ConclusionThis experiment has manufactured the anti-glomerular basement membrane glomerulonephritis rat model successfully, Application of neutralizing monoclonal antibodies (MAbs) of anti-GBM antibody against anti-GBM glomerulonephritis rat model of early intervention can significantly reduce the crescent body, reducing the degree of glomerular sclerosis, improves the renal function in rats. Mabs primarily through with circulating pathogenic anti-GBM antibody of anti-GBM glomerulonephritis rat model specific binding and to prevent some of the antibodies deposition in the GBM, inhibit cell proliferation within the renal glomerulus and crescent formation.

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CLC: > Medicine, health > Surgery > Urology ( urinary and reproductive system diseases) > Kidney disease > Nephritis
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