The Protective Effect Of L-caranitine On Renal Fibrosis In Rats With Unilateral Ureteral Obstruction

Objective:To investigate the protective effect of 1-carnitine(LC)on renal fibrosis in Unilateral Ureteral Obstruction(UUO)rats and its mechanism.Methods:Forty male Sprague Dawley rats aged 7 weeks and weighing between 220g and 250g were selected and randomly divided into sham operation group,model group and treatment group(8 rats in each group).Sham operation group(Sham):left ureter without ligation and intraperitoneal injection of 0.5ml/d normal saline;Model group:left ureter was ligated and intraperitoneal injection of 0.5ml/d normal saline was performed.Treatment group:left ureteral ligation and LC 200g/kg/d intraperitoneal injection.After 1 week and 2 weeks of the experiment,the rats were placed in a metabolic cage,and their water intake,24 hours' urine volume and body weight were measured.The rats were immediately sacrificed,and blood samples were collected.Scr and BUN were determined by an automatic biochemical analyzer.Renal tissue sections were taken and the renal tubular interstitial fibrosis(tubulointe-rstiffi-brosis,TIF)was observed by Masson staining.TUNEL staining was used to observe apoptosis.The expression of MnSOD,TGF-?1,CTGF and SDHA were detected by western blot.Results:1.In the UUO model group,the renal morphology changed after 1 week of obstruction,and the color became lighter,with obvious swelling and enlargement,a large amount of fluid in the renal pelvis,and the renal parenchyma became thinner.The above changes were more obvious after 2 weeks.There were no significant differences in body weight,24-hour urine volume and renal function between the UUO group and the sham group(P>0.05).Compared with the model group,there were no significant differences in body weight,24-hour urine volume,and renal function indexes between the treatment group and the model group(P>0.05).2.Compared with the sham operation group,the percentage of TIF was significantly increased by Masson staining in the UUO 1-week group.Compared with the UUO1 group,the TIF percentage of the UU02 group increased significantly.Compared with UUO1-week group,TIF percentage in UUO+LC1 group decreased significantly.Compared with UU02 group,TIF percentage of UUO+LC2 group decreased significantly.AIl had statistical significance(P<0.05).3.The number of TUNEL staining positive cells in UUO1 group was significantly increased compared with the sham operation group.TUNEL staining positive cells increased in UU02 group compared with UUO1 group.TUNEL positive cells were decreased in UUO+LC1 group compared with UUO1 group.Compared with UU02 group,the number of positive cells in UUO+LC2 group decreased.All had statistical significance(P<0.05).4.MnSOD expression in the UUO1-week group was significantly lower than that in the sham group.Compared with the UUO1-week group,the expression of MnSOD in the UU02-week group decreased significantly.MnSOD expression was significantly increased in UUO+LC1 group compared with UUO1 group.MnSOD expression in UUO+LC2 group was significantly higher than that in UU02 group.All had statistical significance(P<0.05).5.SDHA expression in the UUO1-week group was significantly lower than that in the sham group.Compared with the UUO1 group,the SDHA expression in the UU02 group decreased significantly.Compared with UUO1-week group,SDHA expression was significantly increased in UUO+LC1 group.Compared with UU02 group,SDHA expression was significantly increased in UUO+LC2 group(P<0.05).6.The expression of TGF-1 in the UUO1-week group was significantly higher than that in the sham group.Compared with the UUO1-week group,MnSOD expression was significantly increased in the UU02-week group.Compared with the UUO1-week group,the expression of MnSOD was significantly decreased in the UUO+LC1 group.Compared with UU02 group,MnSOD expression in UUO+LC2 group decreased significantly.All had statistical significance(P<0.05).7.The CTGF expression in UUO1-week group was significantly higher than that in the sham group.Compared with the UUO1-week group,the CTGF expression was significantly increased in the UU02-week group.Compared with UUO1-week group,CTGF expression was significantly decreased in UUO+LC1 group.Compared with UU02 group,the CTGF expression was significantly decreased in UUO+LC2 group.All had statistical significance(P<0.05).Conclusion:L-carnitine has a protective effect on renal fibrosis in rats with unilateral ureteral obstruction,and the mechanism may be related to 1-carnitine's anti-oxidative stress,anti-apoptosis and anti-mitochondrial oxidative damage.