Effects Of Contrast Media On Oxidative Stress And Na~+, K~+-ATPase Activity In Proximal Tubles In Kidney Of Rats

Objective:The present study was designed to explore the effect of contrast media on oxidative stress and Na+-K+-ATPase activity in proximal tubles (PT) of kidney in rats and to investigate the pathogenesis of contrast-media induced nephropathy(CIN).Methods:Fifty-four rats were randomly divided into three groups:high-osmolar contrast media, low-osmolar contrast media group and control group. Contrast media were injected between high-osmolar contrast media (HC group) and low-osmolar contrast media (LC group) by caudal veins of normal rats according to 10ml/kg, equivalent saline was injected in control group (NS group). Samples were obtained on the second, third and seventh day. Different doses of high-osmolar contrast media 5ml/kg (LG group), 10ml/kg (MG group),15ml/kg (HG group) were injected by caudal veins in eighteen normal rats, and samples were obtained after 72 hours. Diabetic rats model establishment was made by Single transperitoneal Streptozotocin solution (STZ,55mg/kg) in eighteen rats, they were randomly divided into three groups:HD (high-osmolar contrast media), LD (low-osmolar contrast media) and ND group (equivalent saline), and samples were obtained after 72 hours. PT determination of Na+,K+-ATPase activity was performed by liquid scintillation counter using radioimmunoassay. Serum and kidney tissues Maleic dialdehyde (MDA) concentration of rats were detected by the method of thibarbituric acid. Serum and kidney tissues superoxide dismutase (SOD) level of rats were detected by thibabituric acid method. Localization and expression of inducible nitric oxide synthase (iNOS) protein in kidney tissues were observed by immunohistochemistry staining method.Results:Serum creatinine level of contrast media injection rats increased obviously (P<0.05), there was no significant difference between in HC and LC group on serum creatinine level. Compared with NS group, Na+,K+-ATPase activity of PT decreased significantly in LC and HC group (P<0.01), no significant difference was found between LC and HC group. In HD and LD groups, Na+,K+-ATPase activity of PT decreased markedly in NS, LC and HC group. Moreover, Na+,K+-ATPase activity of PT in HD group was much lower than that of LD group (P<0.01). Compared with NS group, the activitiy of SOD decreased significantly in LC and HC group (P<0.05, P<0.01), MDA concentration increased markedly in LC and HC group (P<0.05, P<0.01). Expression of iNOS protein was much higher in LC and HC group than that of NS group. (P<0.01). Compared with LC, HC and ND group, expression of iNOS protein was much higher in HD and LD group (P<0.01), and SOD activity was much lower in HD and LD groups than the other three groups (P<0.01). Na+,K+-ATPase activity of PT inverse correlated with serum Scr level. Na+,K+-ATPase activity of PT in HG group than MG and LG group (P<0.01), and kidney function was much worse on the second or third day than the seventh day after contrast media injection (P<0.01).Conclusion:Na+,K+-ATPase activity of PT was inhibited significantly by contrast medium induced rats, especially injection of high dose contrast medium. High-osmolar contrast media might inhibit Na+-K+-ATPase activity of PT severely in Diabetic rats. We presumed that oxidative stress played important roles in pathogenesis of CIN. Kidney function was much worse on the second or third day than the seventh day after contrast media injection.