Effect Of Atorvastatin On Oxidative Stress And Klotho Protein In Rats With Adriamycin Nephropathy

Objective:To investigate the protective effect of atorvastatin on adriamycin nephropathy rats and to investigate whether its possible mechanism is related to oxidative stress and klotho protein expression.Methods:From 60 wistar rats that were 8 weeks old,20 rats were selected as control group without any treatment.and the remaining 40 rats were modeled by tail vein injection of doxorubicin(10 mg/kg).After successful modeling,4 dead rats were eliminated,then the remaining 36 rats were randomly divided into model group and intervention group,18 in each group.Rats in the intervention group were treated with atorvastatin 10 mg/kg daily gavage.Meanwhile,rats in the control group and model group were given normal saline 1ml/kg daily gavage for 12 weeks.To evaluate the damage to the renal system in rats under adriamycin nephropathy,24 hours urine protein quantification and serum albumin quantity were collected and tested in rats at weeks 4?8 and 12.At the same time,six rats were randomly executed in each group at the 4 ?8 and 12 weeks for renal histopathological observation.The expression levels of malondialdehyde(MDA),superoxide dismutase(SOD),and total antioxidant capacity(T-AOC)in the kidney of adriamycin nephropathy rats were measured.The detection indexes were used to evaluate oxidative stress injury in adriamycin nephropathy rats.HE staining of rat kidney and observe the histopathological changes of rat kidney tissue under adriamycin nephropathy.qRT-PCR detection of klotho mRNA expression,Western Blot detection of klotho protein expression.Results:(1)During the same time period,the 24 hour urine protein quantification of rats in the model group was significantly higher than that in the control group,and the urine protein quantification value of rats in the model group increased continuously over time.the 24 hour urine protein quantification in rats in the intervention group was also higher than that in the control group,but lower than that in the model group,the difference was statistically significant(F=242.285?1412.89,P<0.05).(2)During the same time period,the serum albumin quantity in the model group was lower than that in the control group,and the serum albumin value continued to decrease over time.serum albumin values in the intervention group were lower than in the control group but slightly higher than in the model group.the difference was significant(F=58.265?240.54,P<0.05).(3)The model group and the intervention group were found to have slight enlargement and dark color.HE staining light microscopy revealed edema in the renal tubule epithelium and no structure insome renal regions.But the edema of renal tubular epithelial cells was alleviated in the intervention group,and the lesion degree was less than that in the model group.(4)During the same time period,the oxidative stress index of rats in model group and intervention group MDA increased,but the MDA of intervention group was lower than that in model group.On the contrary,oxidative stress index SOD and T-AOC expression decreased in the model group and the intervention group,and were lower than those in the normal control group.While after atorvastatin treatment,the SOD and T-AOC values of the intervention group were slightly higher than those of the model group(MDA: F=20.43?161.64,P<0.05;SOD:F=10.25?98.61,P<0.05;T-AOC:F=4.97?604.10,P<0.05).(5)During the same time period,the expression of klotho mRNA and klotho proteins decreased in the model group and the intervention group compared with the control group.The expression of klotho mRNA and klotho protein was increased in rats after atorvastatin intervention.Differences were significant(qRT-PCR : F=253.21?964.23,p<0.05;Western Blot :F=173.88?821.6,P<0.05).Conclusions:(1)Atorvastatin can improve the progression of renal disease in rats with adriamycin nephropathy due to kidney injury;(2)Renal damage in rats with adriamycin nephropathy may be related to oxidative stress.In adriamycin nephropathy,the results of MDA increased and SOD?T-AOC decreased,while atorvastatin can improve its abnormal expression;(3)The expression of klotho mRNA and klotho protein in adriamycin nephropathy was decreased.But it was increased with adorvastatin intervention,suggesting that the mechanism of adriamycin nephropathy may be related to oxidative stress and decreased expression of klotho protein.Atorvastatin may reduce renal damage in adriamycin nephropathy rats by increasing klotho protein expression.