ABSTRACT
Objective To investigate the correlation between nuclear factor(NF)-?B and inflammation of cell in adriamycin-induced nephritic rats,and the intervention of antisense oligonucleotide targeting NF-?B to adriamycin-induced nephritic rats by measuring the expression of NF-?B p65 in renal cortex and the secretions of interleukin-6(IL-6),tumor necrosis factor-?(TNF-?)in serum.Methods Thirty male SD rats were divided into 5 groups(6 rats in each group):group A(sham operation),group B(glomerulosclerosis),group C(sense oligonucleotide),group D(non-sense oligonucleotide),group E(antisense oligonucleotide).Glomerulosclerosis models were made for SD rats by unilateral nephrectomy and being injected with adriamycin into caudal vein.In the 8th week,various medicine applys to correspon-ding group for intervention.At the 4th day and 8th day after intervention,the excretion amounts of 24 hours urine protein were determined.Hematoxylin-Eosin(HE) staining was used to observe the renal pathological changes.Using image analysis system to calculate glomerulosclerosis index(GI).The expression of NF-?B p65 in renal cortex was measured by immunohistochemistry staining,the secretions of IL-6,TNF-? in serum were performed by means of enzyme-linked immunosorbnent assay,respectively.Results At different time points,the expressions of active-NF-?B p65,IL-6,TNF-? in group E were significantly lower than those in group B.The intervention effects of antisense oligonucleotides at the 8th day were stronger than that at the 4th day.Conclusions NF-?B is significantly correlated with glomerulosclerosis and inflammations of glomerular intrinsic cells.Using NF-?B antisense oligonucleotide to be injected into renal artery can block directly the translation of NF-?B gene,delay inflammations of glomerular intrinsic cells and the progressions of glomerulosclerosis.
ABSTRACT
Objective To investigate the effect of antisense oligodeoxynudeotides(ODN)targeting nuclear factor ?B(NF-?B)on the expressions of Caspase-3 and NF-?B in glomerulosclerosis.Methods Male SD rats were divided into 3 groups:sham operation(group A,n=6),glomerulosclerosis(group B,n=6),intervention(group C,n=9).Group C was divided into 3 groups:sense ODN(group C1,n=3),non-sense ODN(group C2,n=3),antisense ODN(group C3,n=3).Glomerulosclerosis models were made for SD rats by unilateral nephrectomy and being injected with adriamycin into caudal vein.After 8 weeks,various ODN applied to corresponding group for intervention.At the end of the 9th week,kidneys were taken out from all rats for the measurement of expressions of NF-?B p65 and Caspase-3 by immunohistochemistry staining.Results After intervention,on the d7,the rats urine protein,glomerular sclerosis index(GI)and expressions of Caspase-3,NF-?B p65 in group C3 were significantly lower than those in group B,C1,C2(Pa0.05).Conclusion Antisense ODN targeting NF-?B can inhibit the activities of NF-?B,Caspase-3 in rats kidneys and retard glomerulosclerosis and glomerular intrinsic cell apoptosis.