Study On The Correlation Between 8-hydroxy-2′-deoxyguaosine And Renal Interstitial Fibrosis

Objective: To analyze the relationship between 8-hydroxy-2’-deoxyguaosine(8-OHdG)and the progress of renal interstitial fibrosis(RIF),and to investigate the possible role of oxidative stress(OS)in the pathogenesis and development of RIF in UUO rats.Methods: A total of 48 male SD rats were randomly divided into UUO model group(UUO group)and Sham operation group(Sham group),24 rats in each group.At the 3,7,14 and 21 days after operation,6 rats were sacrificed,and the serum,24 hours urine and kidney tissue samples were collected.Determination of blood urea nitrogen(BUN),serum creatinine(Scr);renal pathological changes were observed with hematoxylin / eosin(HE)staining and Masson staining;enzymelinked immunosorbent assay(ELISA)method was used to detect the serum and urine 8-OHdG,transforming growth factor beta-1(TGF-β1);Spectrophotometric Determination of serum total superoxide dismutase(T-SOD),glutathione peroxidase(GPx)and malondialdehyde(MDA).Results:(1)Compared with group Sham,the tubulointerstitial damage of UUO group rats was worse and prolonged with the course of disease.It showed the typical UUO model feature of acute renal tubular injury and interstitial fibrosis were successfully created.(2)Compared with the Sham group,the left kidney weight,blood urea and creatinine in the UUO group increased significantly at the 3rd day,7th day,14 th day and 21 st day(P < 0.05).(3)The change of fibrosis index: the level of serum TGF-β1 at different time points of UUO group were significantly higher than Sham group(P < 0.05)(4)The changes of oxidative stress indicators: the serum T-SOD of UUO group at 7 days after operation was higher than that of Sham group(P < 0.05),however,there were no significant differences at the 3rd day,14 th days and 21 st days;between the two groups.the serum level of GPx in UUO group at the 14 th days,21 st days after operation were statistically significantly decreased than that of the 3rd day,7th day(P < 0.01).The blood and urine 8-OHdG in group UUO at the 21 st days were higher than that in group Sham(P < 0.01),but there was no significant difference between the two groups at other time points.There were no significant difference in serum MDA,T-SOD and urine 8-0HdG at each time point.(5)Correlation analysis showed that serum 8-OHd G was positively correlated with serum TGF-β1(r = 0.485,P = 0.016)and serum MDA(r = 0.419,P = 0.042),and negatively correlated with renal interstitial fibrosis score(r =-0.503,P = 0.012).Conclusions:1.The OS may participate in the progression of RIF in UUO rats by affecting the level of TGF-β1.2.Serum 8-OHdG which is the main metabolite of DNA oxidative damage in OS process was related to the progression of RIF in UUO rats.