The Inhibitory Effect And The Mechanism Of Piperazine Ferulate On The Renal Interstitial Fibrosis Of Rat UUO Model

Objective: The renal interstitial fibrosis(RIF) is the common pathway by which all kinds of chronic kidney diseases progress to the end stage renal disease . Piperazine Ferulate is distilled from Szechwan Lovage Rhizome and compounded further, it has been confirmed that it can treat diabetic nephropathy and Adriamycin nephropathy. In this study, we want to observe whether Piperazine Ferulate can defer the progress of the renal interstitial fibrosis of unilateral ureteral obstruction (UUO) rats , and then to explore its mechanism.Methods :48 male rats were randomly assigned into sham-operated rats group(SOR group), unilateral ureteral obstruction model group (UUO group), ARB-treated group(ARB group) and Piperazine Ferulate- treated group(PF group).From the day before operation, ARB and PF groups were administrated daily by intregastric administration(ia) respectively at the dose of Losartan 20mg/kg and Piperazine Ferulate 100mg/kg each day. UUO and SOR groups were administrated a certain volume of saline by ia. On the operation day, the 7th day and 14th day after operation, we weighted all the rats. On the 7th day and 14th day, 6 rats which were selected randomly from each group were killed. The levels of 24-hour urine protein and serum creatinine were examined at each time point. We observed the pathologic change of the kidney and detected the expression levels of TGF-β1,α-SMA,FN and ColI by immunohistochemistry and RT-PCR at each time point.Results:(1) There was no significant difference in the level of 24-hour urine protein among each group at the same time point(P>0.05). (2)The level of serum creatinine in UUO group was obviously higher than those in other groups at day 7, 14(P<0.05); The level of serum creatinine in ARB and PF groups was higher than that in UUO group at day 7,14(P<0.05);there was no significant difference between ARB and PF group at the same time point (P>0.05). (3) The renal pathology stain of SOR group showed no abnormalities; The damage of the interstitium of UUO group was heavier than that of SOR group and treatment groups at same time point.(4) Immunohistochemistry and RT-PCR showed that there were slightly basal expression of TGF-β1,a-SMA, ColI and FN in SOR group ,and the expression of the above indexes in UUO group on the 7th day and 14th day were significant increased (P<0.05) ; The expression levels of TGF-β1,a-SMA,ColI and FN in PF and ARB groups were lower than that in UUO group at the same point (P<0.05) .Conclusion:Piperazine Ferulate can partly delay the progress of renal interstitial fibrosis in UUO rat model, its mechanism may be related to suppressing the expression of TGF-β1 and a-SMA and reducing the composition of ColI and FN.