The Relation Of Histone Deacetylase1 , 2 And Fibrotic Tubuloin-terstitium In Kidney And The Research Of Interfering The Drug

Objective This is a research to observe the trend,relevance and potential pothgentic significance of Histone deacetylase(HDAC1,HDAC2) and transforming growth factor-β1(TGF-β1) in the course of tubulointerstitial fibrosis in kidneys of young rats with unilateral ureteral obstraction (UUO), and the interfering effects of the treatment with sodium Valproate which is the inhibitor of Histone deacetylaseⅠ.Methods Young SD male rats with unilateral ureteral obstruction(UU0) were served as experiment models. All of the 3-4 weeks old rats were randomly divided into three groups,which were model group after UUO(UUO group,n=30),treated group after UUO(Valproate group,n=30),and sham operation group(control group,n=30).At the days points of1,3,5,7,14,the degree of tubulointerstitial injury of the there groups were evaluated by using HE and Masson staining. At the same time,the expression ,localization of HDAC1,HDAC2 and TGF-β1 and correlation among them were detected by immunohistochemistry staining.Finally,we evaluated function of HDAC1,2 in the renal tubulointerstitial fibrosis. All the data of experiment were analyzed by statistics software SPSS13.0.Results(1) Morphological changes:At day 1,the part of the tubule is dilated in UUO group .At day 3,dilated tubule, slight inflammatory cells which infiltrated into renal tissues ,and swelling of tubular epithelial cells were observed in UUO group. It was showed obviously at day 7,more tubule were dilated;generous inflammatory cells infiltrated into renal tissue, cellulose exudation happened.At day 14, tubulointerstitial fibrosis is broaden. With the experimental session continuing ,pathological changes in tubulointerstitial were becoming more and more serious in UUO group. Compared with control group,there were difference significance in different time points .The extent of tubulointerstitial pathological changes in Valproate group is more alleviative than the UUO group(P<0.05),but still more serious than the control group(P<0.05).(2) Expression of HDAC1,HDAC2 and TGF-?1 proteins:①Immunohistochemical staining indicated that HDAC1 and HDAC2 were expressed slightly in nucleus of tubule epithelial cellular and glomerular cell.TGF-?1 proteins were expressed slightly in tubule epithelial cellular of control group,and almost no exist in tubulointerstitial regions and glomerular. There was no difference in all the time points(P>0.05).②Compared with control group, the level of expression of the HDAC1 and HDAC2 proteins were increased gradually.HDAC1 and HDAC2 came to peak at day 7,and gradually decreased at day 14,but still more than that of the control group(P<0.05). The expression of TGF-β1 were intensivly increased with the extension of the duration of the experiment. Much more intensive expression of TGF-β1 were observed than the control group(P<0.05)At each time point the difference in UUO groups was significant(P<0.05).③T he tendency of those factors'expression was inhibited in each Valproate group(P<0.05),but still higher than control group(P<0.05).The significant difference were observed between UUO group and Valproate groups in different time points(P<0.05). At each time point the difference in Valproate groups was significant(P<0.05). (3)Correlation analysis:Positive correlations were observed among the observived factors(P<0.01)ConclusionIn the course of tubulointerstitial lesions with young rats, the up-regulated expression of HDAC1,HDAC2 and TGF-β1 exhibit a great significant sense,HDAC -s maybe induce TGF-β1 synthetics to accelerate tubulointerstitial fibrosis ;while sodium Valproate treatment have a visible interfering effects.