| Background:contrast media-induced acute kidney injury(CIAKI) has become the third common cause of hospital-acquired acute kidney injury.There is growing evidence suggests that reactive oxygen species (ROS) play an important role in CIAKI and NADPH-oxidase is a major source of ROS production.Mitochondria-targeted peptides can scavenge ROS,reduce mitochondrial ROS production and inhibite lipid peroxidation. However, It is not clear whether mitochondria-targeted peptides protect CIAKI.Objective:To explore the role of oxidative stress,NADPH-oxidase and mitochondrial energy metabolism in CIAKI rats with environment of hypercholesterolemia and to investigate the protective effect of mitochondria-targeted peptides (MTP131,SPI20).Methods:Forty healthy SD male rats were randomly divided into normal dietary group (group NN, n= 8) and high cholesterol supplemented dietary group (group H,4% cholesterol and 1% cholic acid,n=32).At the end of 8 weeks,one of normal group was too weak to survive,four rats with high cholestoral diet lost weight and finally died, the remains with high cholesterol diet were randomly divided into four subgroups (7/group),namely high cholesterol diet group(group HN),high cholesterol plus contrast media diatrizoate group (group HH),high cholesterol plus diatrizoate plus MTP131 group(MTP protective group, group HM),high cholesterol plus diatrizoate plus SPI20 group (SPI20 protective group,group HS).Seven rats from each diet feeding were given a tail vein injection of either diatrizoate with 10ml/kg or equal volume of normal saline,the rats of MTP131 or (SPI 20) protective group were given with MTP131 or SPI 20 (3mg/kg) by peritoneal cavity injection 3 times (24 h before and after contrast media injection and half hour just before contrast media administration).Forty-eight hours before and after contrast media injection,blood and urine samples were prepared to determine total cholesterol,triglyceride,serum, creatinine, creatinine,clearance(Ccr), fractional excretion of sodium and potassium levels.Forty-eight hours after contrast media injection, the rats were executed. The malonadehyde (MDA),superoxide dismutase(SOD), activity of ATPase and NADPH oxidase of kidney tissue were measured. The expression of NOX4 was assessed by Western blot. The renal injury was assessed by HE staining.Results:Before injection of contrast medium, An increase of cholesterol was observed in all rats with high cholesterol diet group. Compare to the group NN, the Scr, renal tubular injury scores and NADPH oxidase activity of kidney tissue increased in the rats of group HN (P<0.05,P<0.001,P<0.001,respectively).In group HH, the Scr, FeNa%,FeK%,MDA level of kidney homogenate were higher and the CCr,renal SOD level, ATPase activity were lower than those of group NN (P<0.01);the renal tubular injury scores, NADPH oxidase activity and expression of NOX4 in kidney tissue were significantly greater than those of group NN (P<0.001,P<0.05,respectively).Compare with the group HN, the Scr, FeNa%, FeK%, MDA level of kidney homogenate,renal tubular injury scores and renal NADPH oxidase activity of group HH also increased (P<0.01),the CCr, renal SOD and ATPase activity decreased and the expression of NOX4 in kidney tissue upregulated (P<0.05).Mitochondria-targeted peptides MTP131 and SPI20 could downregulate level of Scr, FeNa%, FeK% and MDA content in kidney homogenate (P<0.05),upregulate the renal SOD and ATPase activity (P<0.05);The renal tubular injury scores, NADPH oxidase activity and expression of NOX4 were decreased (P<0.001,P<0.05,respectively).Conclusion:Oxidative stress, NADPH oxidase and mitochondrial energy metabolism play an important role in CIAKI rats with environment of hypercholesterolemia. MTP131 and SPI20 might play a protective role in CIAKI rats with environment of hypercholesterolemia, the mechanisms may be related to anti-oxidant, scavenge lipid peroxides, reduce NADPH oxidase activity, suppress the expression of NOX4 protein in kidney and protect mitochondrial ATPase.
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