Effect Of Combination Of Leflunomide And Benazepril On TGF-β1and Ctgf Expression In The Renal Tissues Of Rats With Diabetic Nephropahty

Objective:To observe the effect of combination of leflunomide and benazepril on the Biochemical index and the expression of Transforming Growth Factor beta1(TGF-β1) and Connective Tissue Growth Factor(CTGF) in diabetic nephropathy rats model.to explore for the inflammation mechanism and treatment of diabetic nephropathy.Method:Fifty five health adult male Wistar rats were randomly divided into five groups:Normal control group (NC, N=7); model group (DN, N=12);benazepril treated group (N=12); leflunomide treated group(N=12) and combination treated group(benazepril+leflunomide, N=12).The rat model of Diabetic Nephropathy was induced by injection of Streptozotocin (STZ,65mg/kg),rats of NC were injection of citrate buffer solution. After model established,Benazepril treatment group was intragastric administered with benazepril (10mg/kg/d), leflun-omide treatment group was intragastric administered with leflunomide (10mg/k g/d),and combination treatment group was intragastric administered with benazep-ril (lOmg/kg/d) and leflunomide (10mg/kg/d);The same amount of water was fed in model and normal control group.The fasting blood glucose(FBG),body weigh-t,Serum creatinine,Urine creatinine and24-hour urinary protein excretion (24UPE) were detected in the end of4th,8th and,12th weeks,Then calculate the creatnine cle-arancerate (Ccr) and kidney weight/body weight(KW/BW). At the end of12th we-eks, The expression of transforming growth factor-betal (TGF-β1) and connective tissue growth factor(CTGF) in renal tissue of diabetic nephropathy rats were obs-erved by immunohistochemical assay.Results:(1) The levels of FBG in DN model group and treatment groups were signific-antly higher than those in NC group(p<0.01),There is no statistical differences among DN model group and treatment groups.(2) The body weight in DN model group and treatment groups were significantly lower than those in NC group(p<0.01).(3) Compared with NC group, the kidney weight and KW/BW were significantly increased in other groups(p<0.01); Compared with the same period DN model group, t-he levels of KW/BW were decreased in treatment group(p<0.05), especially in combi-nation treatment group(p<0.01).(4) Compared with the same period NC group,the leve-ls of24UPE were significantly increased in DN model group and treatment groups (p<0.01);At the end of the8th week,the level in combination treatment group were low-er than the same period DN model group(p<0.05);At the end of12th week the level in all treatment groups were lower than the same period DN model group(p<0.05).(5) Co-mpared with the same period of NC group,the levels of Ccr were significantly increa-sed in treatment groups(p<0.05); At the end of12th week,the level of Ccr in combina-tion treatment group were decreased than DN model group(p<0.05).(6) In DN group,T GF-β1and CTGF expression was significantly increased in mesangial region of glom-erulus (p<0.01, compared with NC group); the increases were attenuation in treatment groups, especially in combination treatment group(p<0.05).Conclusions:(1) Combination of benazepril and leflunomide can significantly reduce t-he TGF-β1and CTGF expression in mesangial region of glomerulus in DN rats.(2) Co-mbination of benazepril and leflunomide can delay the progress on DN, and the effect is superior to benazepril or leflunomide alone.