Effect And Mechanism Of Qijing Yishen Decoction On Nrf2/HO-1 Signaling Pathway In Diabetic Nephropathy Rats

Objective To investigate whether Qijing Yishen Decoction(QJYSD)can protect renal from oxidative stress injury by regulating Nrf2/HO-1signaling pathway in diabetic nephropathy(DN)rats.Methods Diabetic rat model was prepared by high-fat and high-sugar diet combined with a small dose of one-time streptozotocin injection.The experiment was divided into normal control group,model group,QJYSD low-,medium-and high-dosage groups(5.76g/kg·d,11.52g/kg·d23.04g/kg·d)and valsartan group(30 mg/kg·d).After 12 weeks treatment,general situation indicators and fasting blood glucose(FBG)were measured.Samples of urine,blood and kidney tissues were collected and used for detection,including 24 h urine total protein(24h UPro),glycated serum protein(GSP),serum creatinine(SCrea),blood urea nitrogen(BUN),histopathology(HE staining,Masson staining),oxidative stress injury indicators(Superoxide dismutase(SOD)activity,MDA(Malondialdehyde)content).The expression levels of Nrf2,HO-1,FN in kidney tissues were detected by Western blot and FN protein deposition was detected by immunohistochemistry.Result In comparison with normal group,I ntake of food(Food Inter)and water(Water Inter)were increased and weight was decreased in the model group(P<0.01);the levels of RI,24 h UPro,FBG,GSP,SCrea and BUN were significantly increased in the model group(P<0.01);glomerular volume,mesangial area,renal interstitial inflammation and collagen volume ratio were significantly increased in the model group(P<0.01);content of serum MDA were increased and activity of serum SOD were decreased in the model group(P<0.01);the expression levels of total Nrf2,HO-1,Nrf2,FN protein and the deposition of FN protein in the kidney were significantly increased in the model group(P<0.01).In comparison with the model group,Food Inter and Water Inter were decreased in the different dosage group of QJYSD in a dosage dependent manner and valsartan group(P<0.05,P<0.01);the levels of RI,24 h UPro,FBG,GSP,SCrea,BUN were decreased in a certain extent(P<0.05,P<0.01);glomerular volume,mesangial area,renal interstitial inflammation and collagen volume ratio were decreased(P<0.05,P<0.01);content of serum MDA were decreased and activity of serum SOD were increased(P<0.05,P<0.01);The expression levels of total Nrf2,HO-1,nuclear Nrf2,FN protein and the deposition of FN protein in the kidney were significantly decreased(P<0.05,P<0.01).In comparison with the valsartan group,the levels of FBG and GSP,protein expression levels of HO-1 and Nrf2 in renal tissues were decreased(P<0.05,while the levels of FN increased in the high-dose QJYSD group(P<0.05).Conclusion QJYSD can alleviate renal injury,improve renal tissue structure and function,and delay the progression of renal fibrosis by promoting the activation of Nrf2/HO-1 signaling pathway to enhance anti-oxidative in DN rats renal.