The Effect Of Astragalus And Safflower Mixture On Expression Of Plasminogen Activator Inhibitor 1 In Renal Tubulointerstitial Fibrosis In Rats With Unilateral Ureteral Obstruction

Objective:To investigate the expression of PAI-1 in renal tubulointerstitial fibrosis in rats with Unilatreal Ureteral Obstruction.To investigate the theraputic effects and its mechanisms of Astragalus and Safflower mixture.Methods:Rat renal interstitial fibrosis model was produced by unilateral ureteral obstruction,40 Wistar male rats were randomly divided into four groups,10 in each:sham group,UUO group, A&S group and ACEI group.Astragalus and Safflower mixture,ACEI or the same amount of water were administered by gavage beginning 3 days before UUO preparation and continued through forteen days aider UUO.Sera and kidney tissues were collected from each group on the forteenth day.Bun and Scr were measured.It was carded out to measure the level of tubulointerstitial damage by Masson staining.The expression of PAI-1 and fibronectin(FN)in kidneys was analyzed by immuno-histochemical method.Result:1.The renal tissue were stained with HE.There was no changed in sham group.But in UUO group,it was shown that there was tubular epithelial cells denaturalization,renal tubular expand or atrophy,interstitial macrophage and monocyt infiltration,interstitial expand,and there was no glomeruli change.While the change in A&S group and ACEI group were lighter than that in UUO group.The renal tissue Massonstainning showed that there was interstitial expand,fibrous tissues proliferation and there was no glomeruli change.While the change in UUOA and UUOE group was slighter than that in UUO group.Pathologic image analysis shows that the renal interstitial fibrotic area expanded markedly in UUO group.Compared with UUO group,fibrotic area of UUOA and UUOE group was decreased markedly.There was no significant difference betweem UUOA group and UUOE group.2.The level of BUN and Scr in UUO group were significantly highter than that in sham group(P＜0.01).Compared with UUO group,the level of BUN and Scr in A&S group and ACEI group were significantly lower (P＜0.01).There was no significantly difference in these two groups(P＞0.05).3.The protein expression of PAI-1 and FN and the renal interstitial fibrotic area were highter significantly than that in sham group(P＜0.01).Compared with UUO group,those of the treatment groups decreased markedly(P＜0.01).There was no significant difference between A&S group and ACEI group(P＞0.05).4.Correlation of PAI-1 and FN was positive,correlation of PAI-1 and fibrotic area and BUN was positive correlation,correlation of PAI-1 and fibrotic area and Scr was positive correlation.Conclusion:1.PAI-1 upregulated significantly in kidney in the process of renal tubular damage and interstitial fibrosis in UUO rats.2.Astragalus and Safflower mixture can downregulate the level of BUN and Scr in UUO animal model rats,and protect renal function.3.Astragalus and Safflower mixture can suppress the upregulation of PAI-1 and FN expression in kidneys of UUO animal model rats and decrease their interstitial fibrotic area.It is inferred that it may be one of the mechanisms of Astragalus and Safflower mixture suppressing renal tubular damage and interstitial fibrosis.