Comparison Of Contrast Induced Acute Kidney Injury Between Rat Models Of Drug-Injured And Diabetic Nephrosis

Objective: To investigate the method of the establishment of animal models,we establish two kinds of rat models of contrast-induced nephropathy by drug-Injured and diabetic nephropathy,and to compare their respectively of characteristics by using biochemistry and histopathology.Methods:80healthy Sprague-Dawley rats were used to establish two kinds of rat models.40male Sprague-Dawley rats were randomly divided into four groups, control group (N1group, n=10), contrast medium group (CM1group, n=10), renal injury group (S group, n=8) and contrast-induced nephropathy group (M group, n=8). Following a24huor dehydration, rats were injected with iv indomethacin (10mg/kg) and iv L-NAME (10mg/kg)15min apart. After15min, diatrizoate (DTZ10ml/kg) was injected into femoral vein. Another24hour dehydration, rats were sacrificed. Another40male Sprague-Dawley rats were randomly divided into four groups, control group (N2group, n=10), contrast medium group (CM2group, n=10), diabetes mellitus group (DM group, n=10) and contrast-induced nephropathy group (DCM group, n=8). DM group and DCM group rats were given an intraperitoneal injection of60mg/kg streptozotocin (SZT). After8weeks of the establishment of diabetes mellitus, rats were injected with iv diatrizoate (DTZ10ml/kg) for two consecutive days by femoral vein. Following a24huor dehydration, rats were sacrificed. After all the rats were sacrificed, the venous blood was obtained to examine the serum creatinine (Scr), urea, uric acid (UA) and calculate the creatinine clearance (Ccr) and Kcr; glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), total superoxide dismutase (T-SOD)and malonaldehyde (MDA) in renal cortex and medulla were were measured.as well as the histopathology, the expression of caspase-3and caspase-9were observed.Results:(1) In the model of CIN by drug-Injured,1rat died in S group and2rats died in M group. The results show the level of Scr, Ccr and Kcr were similar between the four groups before modeling. Dehydration of1day, levels of Ccr and Kcr decline in S group and M group than N1group and CM1group.This shows the rat’s renal function has been affected after dehydration of1day. When executed, levels of serum Urea and UA were similar between N1group and CM1group, but they were significantly higher in S group and M group than N1group and CM1group, and the level of serum Urea was significantly higher in M group than S group. Level of microalbuminuria was significantly higher in M group than S group. Compared before and after modeling, all indexes of M group was the most significant in four groups. Pathological results showed the lesions in M group is the most serious than other groups:we can see vacuolar degeneration of renal tubular epithelial cells,some can cause apoptosis,or necrosis, loss to the tubular lumen, tubular collapse, we can see tubular compensatory expansion, it is visible that varying degrees of interstitial inflammation cell infiltration, pathological changes in the out medulla are more serious. In renal cortex and medulla, the activity of T-SOD and GSH-Px was significantly reduced in M group than S group,but the activity of MPO and the content of MDA was significantly higher. Immunohistochemical results showes that the expressions of caspase-3and caspase-9were more significantly increased in M group than S group.(2) In the model of CIN by diabetic nephropathy,no rats died. The results show the level of Kcr was significantly higher in DM group and DCM group than N2group and CM2group before modeling. Compared with N2group, the Scr, Urea, UA, MPO activity in renal cortex and medulla were higher and Ccr, Kcr,GSH-Px and T-SOD activity were less in CM2group at death. Compared with DM group, the Scr, Urea, UA, MPO activity in renal cortex and medulla were higher and Ccr, Kcr,GSH-Px and T-SOD activity were less in CM2group at death. In the four groups,we can see similar histological changes and the expression of caspase-3and caspase-9was the most serious in DCM group.Conclusion:(1)The two kinds of rats model of CIN are all successful,and the injury in the model of contrast-induced nephropathy by diabetic nephropathy is more serious.(2) Contrast medium caused the injury by oxidative stress in kidney and apoptosis in renal tubular epithelial cells,and the injury in renal medulla is more serious than renal cortex. Contrast medium may cause the injury by the activation of caspase-9,and further activate caspase-3by cytochrome C pathway.