| ObjectscTo investigate the tide of P65/Rel-A mRNA expression that is an important member of the nuclear transcription factor kappa-B (NF-кB) family, angiotensin receptors(the 1 type ,and 2 type receptor, AT1,AT2) proteins expression, and the relativiy between them in early stage of tubulointerstitial lesions induced by heavy proteinuria in young rats with Adrimycin nephrosis . meanwhile, to evaluate potential pathogenic role of these factors on aggravated lesions and the interfering effects after treatment with angiotensin converting enzyme inhibitor(ACEI) Benazepril and ACEI combined with angiotensin type I receptor angonist(AT1RA) Losartan .Methods: Wistar female young rats which the years old at 4 weeks were served as the experiment subjects. 20 rats which undergone sham operation and injected with 0.9% NaCL only were used as control group. 60 rats were nephrectomized the left kidney and then injected with adrimycin via intraperitoneal cavity for three times, we validated this model by through to detect and evaluate the blood biochemical and urine parameters and the renal pathologic changes, when the model was established successfully, All of them were randomly divided into three groups, that is untreated group ; ACEI treated group and ACEI+AT1RA treated group. At different time points oftreated for 1,2,3 weeks, we collected the 24h urine and plasma or serum to measure the urinary protein and blood biochemical parameters, and killed six rats at each time point in each group and obtained the renal tissues to detect P65/Rel-A mRNA and AT1,AT2 protein expression by in situ hybridization and imrmmohistological ways respectively. The relativity between AT1,AT2 and P65/Rel-A expression, and the effects of interfering treatment were evaluated.Results: In the early phase tubulointerstitial lesions, following adrimycin injection and proteinuria aggravated progressively, the tendency of inflammatory cells infiltrated into renal tissues, especially in tubulointerstitial regions were increased markedly. The tubule epithelial cells swelling, tubulointerstitial ares to broad, and proteinuria casts in tubule were observed. Compared with control, these changes have difference significantly. At same time, the renal function of rats in untreated group was injured progressively, but the other biochemical parameters in blood were normal all at this time. In situ hybridization and immunochemical staining shown ATI and AT2 protein expressed in tubule epithelial cellular plasm and nuclear membranes (ATI: 1th week 19.82±1.06%, 2th week 25.02±2.59%, 3th week 37.09±1.04% (control: 10.31±0.81%, 10.44±1.55%,10.15±1.49%); AT2:27±1.86%, 9.68±1.42%,12.50±1.93%(control:2.63il.25%±3.12±1.04%,2.66±0.63%), and P65/Rel-A mRNA expression in same location were up-regulated. P65/Rel-A translocation from plasm into nuclear increased markedly simultaneously. The positive signals of hybridization in cytoplasm converted into nuclear gradually. Above all of these were focused in tubulointerstitial regions(lth week 4.04±3.29%, 2th week 34.20±2.43%, 3th week39.89±6.38% (control: 8.51±0.44%, 8.74±0.98%, 8.36±0.89%) .Statistics results has shown a positive correlation between ATI, AT2 and P65/Rel-A expression on localization and time phase ( r=0.857;0.815,P < 0.01=. However, the tendency of those factor's expression were all decreased in each treated groups, the semi quantitative results were that AT1: 14.63±2.12%, 13.73±2.32%, 11.40±1.05%; AT2: 4.41±1.32%, 4.17±1.06%, 3.41±0.81%; P65: 18.46±3.39%, 22.79±1.56%, 26.67±4.88% at 1,2,3 weeks in ACEI treated group; AT1: 12.43±1.46%, 11.14±0.99%, 10.33±0.75%; AT2: 4.21±0.54%, 4.07±1.51%, 3.44±0.61%; P65: 17.87±4.97%, 21.28±5.98%, 22.4612.45% in AT1RA group, respectively. Our results have suggested that the ACEI and AT1RA could inhibite the up-regulation of p65/Rel-A expression and its nuclear translocation from cytoplasm. The significant difference were observed between all groups in different time points (P < 0.05).Conclu...
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