Abstract:OBJECTIVE: To explore the protective effects of bicyclol against renal interstitial fibrosis and possible mechanisms of the protection. METHODS: Eighty-one Sprague-Dawley (SD) rats were randomly assigned to a sham-operated group and UUO groups with and without bicyclol treatment. A rat model of renal interstitial fibrosis was prepared by unilateral ureteral obstruction (UUO). Renal tissues were examined by hematoxylin & eosin and Masson staining on 7, 14 and 21 days. Immunhistochemistry was used for determining plasminogen activator inhibitor-1(PAI-1) expression in the renal interstitium. PAI-1 mRNA expression in renal tissues was semi-quantitatively determined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The relative areas of renal interstitial fibrosis in the bicyclol-treated UUO group 7, 14 and 21days after operation were (9.6±0.6)%, (16.8±0.8)% and (33.6±1.6)% respectively, which were significantly lower than those in the untreated UUO group[(13.0±0.7)%, (25.8±1.5)% and (53.2±2.5)% respectively](P<0.05). The levels of protein and mRNA expression of PAI-1 in the bicyclol-treated UUO group decreased significantly compared with those in the untreated UUO group 7, 14 and 21days after operation (P<0.05). CONCLUSIONS: Bicyclol can alleviate renal interstitial injury and renal interstitial fibrosis caused by UUO in rats, possibly through a downregulation of renal PAI-1 expression.
[2]Gipson DS, Gibson K, Gipson PE, Watkins S, Moxey-Mims M. Therapeutic approach to FSGS in children[J]. Pediatr Nephrol, 2007, 22(1): 28-36.
[3]Li M, Liu GT. Inhibition of Fas/FasLmRNA expession and TNF-alpha release in concanavalin A-induced liver injury in mice by bicyclol[J]. World J Gastroenterol, 2004, 10(7): 1775-1779.
[4]Chevalier RL, Forbes MS, Thornhill BA. Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy[J]. Kidney Int, 2009, 75(11): 1145-1152.
[5]Pang M, Kothapally J, Mao H, Tolbert E, Ponnusamy M, Chin YE, et al. Inhibition of histone deacetylase activity attenuates renal fibroblast activation and interstitial fibrosis in obstructive nephropathy[J]. Am J Physiol Renal Physiol, 2009, 297(4): 996-1005.
[6]Cregger M, Berger AJ, Rimm DL. Immunohistochemistry and quantitative analysis of protein expression[J]. Arch Pathol Lab Med, 2006, 130(7): 1026-1030.
[7]Nangaku M .Mechanisms of tubulointerstitial injury in the kindey: final common pathways to endstage renal failure[J]. Intern Med, 2004, 43(1): 9-17.
[9]Villar SR, Brandoni A, Torres AM. Time course of organic anion excretion in rats with bilateral ureteral obstruction: role of organic anion transporters (Oat1 and Oat3)[J]. Nephron Physiol, 2008, 110(3): 45-56.
[10]Zhang G, Kernan KA, Collins SJ, Cai X, Lopez-Guisa JM, Degen JL, et al. Plasmin(ogen) promotes renal interstitial fibrosis by promoting epithelial-to-mesenchymal transition: role of plasmin-activated signals[J]. J Am Soc Nephrol, 2007, 18(3): 846-859.
[11]Eddy AA. Serine proteases, inhibitors and receptors in renal fibrosis[J]. Thromb Haemost, 2009, 101(4): 656-664.