Influence And Protection Mechanism Of Lycium Barbarum Polysaccharide On Oxidative Stress And Interstitial Fibrosis In UUO Rat

Objective:To observe the effects of different doses of Lycium barbarum polysaccharide(LBP)on oxidative stress and renal interstitial fibrosis in unilateral ureteral obstruction(UUO)rats,and to explore the possible protective mechanism of LBP for renal fibrosis.Methods:A total of 144 healthy adult male SD rats(SPF)were randomly divided into sham operation group,UUO model group,LBP low dose group,LBP medium dose group,LBP high dose group and benazepril group.The UUO model group,LBP low,middle and high dose group and benazepril group all underwent the classical UUO operation.From the second day of the operation,the rats were given continuous intragastric administration for 3 weeks.Among them,the low,medium and high doses of LBP groups were respectively treated with LBP 400mg(kg·d)-1,600mg(kg·d)-1 and 800mg(kg·d)-1;benazepril group administered1.05mg(kg·d)-1,sham operation group and UUO model group were given normal saline by gavage.After 3,7,14,21 days,6 rats in each group were killed.Blood samples were collected to detect serum creatinine(Scr)and the kidney index was calculated.The HE and Masson staining ways were applied to the obstruction side(left)kidney tissues,then the pathological changes was observed under light microscope.The serum Transforming growth factor-β1(TGF-β1),Superoxide dismutase(SOD),Malondialdehyde(MDA)and glutathione peroxidases(GSH-PX)levels were tested by ELISA and colorimetric assay.Results:(1)Compared with the sham group,the Scr and kidney index of Model groups have increased at different degree at each time point(P<0.05),which proved the model is successfully made.(2)Results of HE staining and Masson trichrome staining indicated that left renal tissue structure of the sham operation group is normal.In the UUO model group,the pathological changes of the renal tubules were aggravated with the time prolonging.The inflammatory cell of interstitial infiltration from less to more,focal fibrosis was seen at the 21 st day.(3)Compared with UUO group,the LBP low,medium and high dose groups and benazepril group have decreased kidney index at different degree.At the 7th,14 th,21st days,the LBP low,medium and high dose groups’ serum MDA levels were significance lower than the UUO model group(P<0.05).At each time point,the level of SOD and GSH-PX were higher than the UUO model group(P<0.05)and was highest in the medium dose LBP group.(4)LBP low,medium and high dose groups and benazepril group serum TGF-β1 level was significantly lower than the UUO model group(P<0.05).(5)Compared with model group,the LBP low,middle and high dose group and benazepril group inflammatory infiltration and tubular injury in renal interstitium were milder and the interstitial fibrosis is not heavy.Conclusion:(1)For UUO model rats,LBP can reduce the release of MDA,and increase the production of SOD and GSH-PX.(2)LBP can reduce the pathological injury of UUO model rats and reduce the degree of renal tubular injury and alleviate renal interstitial fibrosis.(3)LBP can decrease the level of serum TGF-β1 and may possiblly inhibit the renal interstitial fibrosis and delay the progression of renal failure.