Effect Of Xiaoyu Xiezhuo Decoction On Oxidative Stress In Rats With Contrast-media Induced Nephropathy Based On Nrf2/HO-1 Signaling Pathway

Objective:To investigate the effect of Xiaoyu xiezhuo decoction on oxidative stress in rats with contrast-media induced nephropathy based on Nrf2/HO-1 signaling pathway.Methods:40 SD rats were randomly divided into normal group,model group,Xiaoyu decoction group and NAC control group,10 rats in each group.The Xiaoyu xiezhuo decoction was given to the rats 7 days before the model building,while the NAC control group received intraperitoneal injection of NAC(150 ug/g)3 days before the model building.After intervention in each group,CIN models were prepared in the model group,Xiaoyu xiezhuo decoction group and NAC control group.Blood samples were collected from the abdominal aorta 24h after the model establishment,and serum creatinine(SCr)and urea nitrogen(BUN)levels were detected.Urine samples were collected from the metabolic cage for 24h,and the levels of NAG and U-y-GT were measured.The histopathological changes of renal tissue were observed by HE staining under optical microscope.Nrf2 and HO-1 were extracted from renal tissue,and the expressions of Nrf2 and HO-1 in renal tissue were detected by Western blotting.Results:After 24 hours of modeling,the levels of serum SCr,BUN,urine NAG and U-y-GT in the model group were significantly higher than those in the normal group(P<0.05).The levels of serum SCr,BUN,urine NAG and U-y-GT in the Xiaoyu xiezhuo decoction group and the NAC control group were significantly lower than those in the model group,but still higher than those in the normal group,with statistically significant differences(P<0.05).There were no statistically significant differences in serum SCr,BUN,urine NAG and U-y-GT between Xiaoyu xiezhuo decoction group and NAC control group(P>0-05).The results of HE staining showed that there were no obvious lesions in the glomeruli,tubules and interstitium of rats in the normal group.The renal tissues of the model group showed extensive vacuolar degeneration of renal tubular epithelial cells,partial tubular necrosis,epithelial cell shedding,obvious tubular protein type,swelling and degeneration of glomerular endothelial cells and epithelial cells,slight increase of mesangial matrix,interstitial edema and inflammatory cell infiltration.Kidney damage in the Xiaoyu xiezhuo decoction group and the NAC control group was reduced to different degrees compared with that in the model group.Slight swelling of renal tubular epithelial cells,partial vacuolar degeneration,partial tubular protein tubule type,and a small amount of inflammatory cell infiltration in renal interstitium were observed.Among them,the improvement was more obvious in Xiaoyu xiezhuo decoction group,with significantly reduced renal interstitial lesion and vacuolar degeneration area of renal tubular epithelial cells and relatively complete morphological structure.Western blotting results showed that the expressions of Nrf2 and HO-1 proteins in renal tissues of the model group were increased compared with that of the normal group,with statistically significant differences(P<0.05).The expression levels of Nrf2 and HO-1 in renal tissues in the Xiaoyu xiezhuo decoction group and the NAC control group were significantly higher than those in the model group(P<0.05).There was no significant difference in the expression of Nrf2 and HO-1 protein between the Xiaoyu xiezhuo decoction group and the NAC control group(P>0.05).Conclusion:Nrf2/HO-1 signaling pathway is involved in the process of acute renal injury in rats with CIN.Xiaoyu xiezhuo decoction can promote the anti-oxidative stress effect by activating this pathway and protect the renal function in rats with CIN.