Research On The Protective Effects Of Total Flavonoids From Smilax Glabra In Rats With Uric Acid Nephropathy And Its Mechanism

Objective This study aimed to investigate the protective effects of total flavonoids from Smilax glabra(TFSG)on preventing renal oxidative damage in rats with uric acid nephropathy by observing its influence on serum uric acid,lipid metabolism,renal function and renal oxidative damage index;to explore the protective mechanism of TFSG on the kidney of rats with uric acid nephropathy by observing its influence on mRNA and protein expressions of renal urate transporters as well as inflammatory cytokines and growth factor on renal tubular epithelial cells.Methods The Sprague-Dawley rats were randomly divided into normal control group,model group,allopurinol group(40 mg/kg),low-dose?medium-dose?high-dose TFSG group(100,300,500 mg/kg).With the exception of normal group,the remaining rats received gavage of adenine(50 mg/kg)with yeast pellets diet simultaneously.Meanwhile,the normal group and model group received gavage of distilled water,and the other groups were given the corresponding drugs.The whole experiment lasted 28 days.At the end of this experiment,the contents of serum uric acid,creatinine(Cr),nitrogen(BUN),total cholestero(TC),triglycerides(TG),albumin(ALB),globulin(GLB),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C),the levels of renal malondialdehyde(MDA),reduced glutathione(GSH)and oxidized glutathione(GSSG),as well as the activities of renal superoxide dismutase(SOD)and catalase(CAT)were detected according to the gulidelines of kits.In addition,histopathological observation were done through renal biopsy in different groups.Simultaneously,the mRNA and protein expressions of renal ATP-binding cassette transporter G2(ABCG2),organic anion transporter 1(OAT1),organic anion transporters 2(OCT2),organic cation/carnitine transporters 2(OCTN2)as well as basic fibroblast growth factor(bFGF),cyclooxygenase-2(COX-2),promoting fibrosis cell factor beta 1(TGF-?1)were detected by fluorescence quantitative PCR and Western blot methods respectively.Results ? By contrasting the normal and model group,the kidney/body weight ratio and the level of UA,Cr,BUN,GLB and TC,TG,LDL-C in the serum of model group were significantly increased,while the level of HDL-C was decreased(P<0.05)compared with normal group;the levels of renal MDA and GSSG in model group were increased,with the SOD,CAT and GSH levels decreased(P<0.05).Moreover,the structures of renal tubular cells in model group were disrupted,showing a tendency of apoptosis.The mRNA and protein expressions of renal ABCG2,OAT1,OCT2,OCTN2 in model group were down-regulated,while the renal bFGF,COX-2,TGF-? were up-regulated(P<0.05)in comparison to normal group.?Compared with model group,TFSG could significantly influence the kidney/body weight ratio,and reduce the concentrations of serum UA,Cr and BUN,the contents of GLB,TC,TG and LDL-C in the serum as well as MDA and GSSG in the kidney of rats with uric acid nephropathy(P<0.05).Moreover,TFSG could significantly increase the level of HDL-C,GSH and increase the activities of SOD and CAT(P<0.05),in which,medium and high dose of TFSG could significantly improve the histopathological changes of kidney in rats with uric acid nephropathy.TFSG was found to up-regulate the expressions of ABCG2,OAT1,OCT2,OCTN2 mRNA and protein(P<0.05),along with down-regulation of bFGF,COX-2,TGF-?1 mRNA and protein expression(P<0.05).The effect of TFSG manifested in dose-dependent manner to some extent.Conclusion TFSG could significantly prevent the renal oxidative damage in rats with uric acid nephropathy,and could regulate the expressions of various renal urate transporters,inflammatory cytokines and growth factors.It has great potential in treating the complications of gout.