The Remedial Study Of AKF-PD On Renal Interstitial Fibrosis In Rats

Background Tubulointerstitial fibrosis is the common pathway in the procedure of all renal diseases leading to chronic renal dysfunction. Anti-fibrotic therapys need to be developed to halt or reverse the eventual progression of renal disease that can progress to end-stage renal failure. AKF-PD is a novel pyridine compound which is synthesized by our own study group. In our previous study, it has been proven that it can significantly inhibit the proliferation of the renal fibroblast and attenuate renal fibrosis. So we decided to carry out animal trial to research effects of AKF-PD on renal interstitial fibrosis after 3 days of the obstruction.Methods Thirty-four female Sprague-Dawley（SD） rats were randomly subdivided into sham-operated group, UUO model group, enalapril-treated group and AKF-PD-treated group, and treated by unilateral ureteral obstruction, but the rats of sham-operated group without ligating or mutilating the ureter of operation. From 3 days to 13 days of the operation, AKF-PD was given 500mg/kg/d by intragastric administration on rats of AKF-PD-treated group, enalapril was given 10mg/kg/d by intragastric administration on rats of enalapril -treated group, and equal volume of vehicle of AKF-PD was given by intragastric administration on rats of UUO model group or sham-operated group daily. After 14 days of the operation, all animals were sacrificed and the obstructed kidneys were collected for HE staining, immunohistochemical staining and RT-PCR.Results fourteen days after obstruction, tubulointerstitial damage index in model group increased （p＜0.01）, and this decreased after treated by enalapril or AKF-PD （p＜0.01）, which were lower in AKF-PD treated group, but without statistical significance; the semi-quantity determination of collagen I protein in model group increased （p＜0.01）, and this decreased after treated by enalapril or AKF-PD （p＜0.01）, which were lower in AKF-PD treated group, but without statistical significance; the semi-quantity determination of TGF-β₁ protein and TGF-β₁ mRNA in model group increased （p＜0.01）, and this decreased after treated by AKF-PD （p＜0.05）; the semi-quantity determination of CTGF protein and CTGF mRNA in model group increased （p＜0.01）, and this decreased after treated by enalapril or AKF-PD （p＜0.05）, which were much lower in AKF-PD treated group （p＜0.01）.Conclusions These results demonstrated that delayed administration of AKF-PD can inhibit renal interstitial fibrosis after 3 days of UUO in rats, and this effect could be realized through decreasing the expression of TGF-β₁ and CTGF in the kidneys.