| Objectives1.To observe the expressions of8-hydroxy-2-deoxyguanosine（8-OHdG）andsuper oxide dimutese（SOD）in diabetic rats kidney injury.2.To investigate theeffect of sitagliptin on the expressions of8-OHdG and SOD in diabetic rats kidney.MethodsSixty-five male Sprague-Dawlry rats were randomly divided into normal controlgroup (NC group, n=15)and model group(n=50). NC group had access to standardchow and water ad libitum, and model group had access to high sucrose-fat diet.Rats were weighed After4weeks. Blood samples from rats were collected and thefast blood glucose(FBG), insulin（FINS）level were assayed. Model group allocatedto be made diabetic received peritoneally injections of streptozotocin (STZ，30mg/kg body weight). NC group received injections of citrate buffer. We includedonly rats with blood glucose concentrations which was not less than16.7mmol/L at72hours after streptozotocin injection in the diabetes group.(3cases died and1case failed to achieve the standard of diabetes mellitus). Then diabetes group ratswere randomly divided into the following three groups: DM group (untreateddiabetes group, n=16), Sita1group (Sitagliptin with the dose of1mg/kg bodyweight daily, n=15), Sita2group (Sitagliptin with the dose of10mg/kg body weightdaily, n=15). DM group and NC group rats were received the equal volume ofphysiological saline. NC group rats were fed with the standard chow, while theremaining three groups were fed with the high fat diet. Rats were weighed at theend of the14weeks. Urine samples for24h were collected to examine urinary protein and8-OHdG. Blood samples were obtained to analysis FBG, FINS, BUN,SCr and SOD. The morphological changes of renal tissues were observed afterhematoxylin-xeosin(HE) staining. Immunohistochemistry staining was used toexamine the expressions of8-OHdG and SOD in the kidney.Results1. At the end of the4th weeks, BW, FBG, FINS, HOME-IR in model groupwere elevated, which were higher than those in NC group (P<0.05).2. Effect on body weight, fasting blood glucose and fasting insulin levels: atthe end of the14th weeks, compared with NC group, BW exhibited significantincreases in DM group and Sita group(P<0.05). However, no significant differencesin BW were encountered between DM group and Sita group (P>0.05). In DM groupand Sita group, FBG significantly increased, while FINS markedly decreased ascompared with NC group(P<0.05). In Sita2group, FBG significantly decreased,while FINS markedly increased as compared with DM group and Sita1group(P<0.05). There were no significant differences in these parameters between Sita1group and DM group (P>0.05).3. Effect on renal function: BUN, SCr and urinary protein for24h in DMgroup and Sita group were significantly higher than NC group(P <0.05). Those inSita1group and Sita2group were significantly lower than DM group (P <0.05).Those in Sita2group were significantly lower than Sita1group (P <0.05).4. Urinary8-OHdG excretion and serum SOD activity: compared with NCgroup, urinary8-OHdG excretion significantly increased while serum SOD activitydecreased in DM group and Sita group(P <0.05). Sita1group and Sita2groupsignificantly suppressed the increase in8-OHdG excretion and attenuated thereduction in serum SOD activity(P <0.05). There were significant differences inthese parameters between Sita1group and Sita2group (P <0.05).5. Effect on renal histology: NC group preserved the normal morphology ofthe kidney. By contrast, glomerular volumes was increased in DM group, accompanied by a significant thickening of glomerular basement membrane andexpansion of mesangial matrix. Those histopathological changes alleviated in Sita1group and Sita2group, and Sita2group was more obviously．6. Effect on immunohistochemistry: compared with NC group, the expressionof8-OHdG in the renal tissue significantly increased while the SOD decreased inDM group and Sita group(P<0.05). Compared with DM group, the expression of8-OHdG significantly decreased while the SOD increased in Sita1group and Sita2group(P<0.05). There were significant differences in these parameters betweenSita1group and Sita2group(P<0.05)．Conclusions1. The8-OHdG expressions of urine and renal tissue increase, while the SODactivity of serum and the SOD expression of renal tissue decrease in the rats modelof diabetes mellitus, suggesting that oxidative stress may take part in thepathogenesis of diabetic kidney injury.2. Sitagliptin has some renoprotective effect on diabetic rats, through down-regulating the expression of8-OHdG and up-regulating the expression of SOD inthe renal tissue. |
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