Localized Expressing Tendenty Of JAK₂/STAT₃ Protein Mediated By Angiotensinâ…¡ Type 1 Recepter Signal On Early Stage Tubulointerstitial Lesions In Unilateral Ureteral Obstruction Young Rats And The Relativity Among Them

Objects:To investigate the tide,relations and potential pothogenic role of JAK₂/STAT₃ protein expression mediated by angiotensin type 1 recepter signal on early stage tubulointerstitial lesions in young rats of Unilateral Ureteral Obstruction(UUO).Meanwhile,to evaluate the interfering effects after treatment with angiotensin coverting enzyme inhibitor(ACEI)Benazepril and angiotensinâ…¡type 1 recepter angonist(ARB)Losartan.Methods:3 weeks old young male Wistar rats(n=72)were chosed as the subjects.All of them were randomly divided into three groups,that was untreated group after UUO(UUO group,n=24),treated group after UUO(UUO+ACEI+ARB group,n=24),and sham operation group(control group,n=24).At the time points that treated for 3,7,14,28 days,six rats were sacrificed in each group and the left renal tissues were obtained to evaluate the renal tissues morphologic changes through HE staining,at the same time we detected the protein expression of AT₁,JAK₂,STAT₃,TGF-β₁ in tubulointerstitial by immunohistochemical ways.Finally,we evaluated the correlation among AT₁,JAK₂,STAT₃ and TGF-β₁ protein expression in localization and time phase.All the data of experiment were analyzed by statistics software SPSS 11.5.Results:(1)Morphological changes:At day 3,dilated tubule,infiltrated into renal tissues of slight inflammatory cells,and swelling of tubular epithelial cells were observed in untreated group after UUO.It was showed obviously at day 7,such as,more tubule were dilated;generous inflammatory cells infiltrated into renal tissue,especially in tubulointerstitial regions;cellulose exudation and tubulointerstitial area broaden.With the experimental session continuing,pathological changes in tubulointerstitial were becoming more and more serious in untreated group after UUO.Compared with control group,there were difference significance in different time points(days 3,7,14 and 28).The extent of tubulointerstitial pathological changes in treated group after UUO is more alleviative than the UUO group(P<0.01),but still more serious than the control group(P<0.01).(2)Expression of AT₁,JAK₂,STAT₃,and TGF-β₁ proteins:â‘ Immunohistochemical staining indicated that AT₁,JAK₂,STAT₃,and TGF-β₁ proteins were expressed slightly in tubule epithelial cellular and glomeruli of control group.There was no difference in all the time points(P>0.05).â‘¡Compared with control group,the level of expression of the four proteins were increased at day 3 in untreated group after UUO,peaked at day 14,and a slight decrease was observed at day 28.And AT₁,JAK₂,STAT₃ and TGF-β₁ protein expression were up-regulated simultaneously in tubular epithelial cells.At the same times,we observed the tide that STAT₃ protein expression transferred from cytoplasm into nucleus.â‘¢The tendency of those factors' expression was inhibited in each treated group(P<0.01),but still higher than control group(P<0.05).The significant difference were observed between treated and untreated groups in different time points(P<0.01).(3)Correlation analysis:Positive correlations were observed among the four factors(r1=0.875,r2=0.897,r3=0.896,r4=0.914,r5=0.873,r6=0.912),(P<0.01).Conclusion:There might be a biologic signal pathway among Angâ…¡,AT₁,JAK₂,STAT₃,and TGF-β₁ in the early phase of tubulointerstitial lesions induced by Unilateral Ureteral Obstruction in young rats,also,it might be one of mechanism that enhanced tubulointerstitial nephropathy;The signal pathway's activity was inhibited by the treatment of Benazepril and Losartan.