| Objective To compare the nephrotoxic levels induced byradiographic contrast media with different osmolarity (HOCM, IOCMand LOCM) in rats with environment of hypercholesterolemia.Todetermine the role of NFκ3 and AgⅡin radiographic contrastnephropathy. The protective role of pentoxifylline was studied.Methods: Forty eight healthy SD male rats with an average weightof into nomal dietary group(NN, n=8) and high cholesterol supplementeddietary group(H, 4% cholesterol and 1% cholic acid,n=40).At the endof 8 weeks,the rats with high cholesterol diet were randomly divided intofive group (n=8/group),which were high cholesterol diet group(HN), highcholesterol diet plus HOCM(76% diatrizoate) group(HH), highcholesterol plus IOCM(Iodixanol) group(HI), high cholesterol plusLOCM (iohexle)group(HL)and high cholesterol plus HOCM pluspentoxifylline group(HHP). 10ml/kg.b.w of the RCM with 300 mg I/mlwere given through a caudal vein in 2 min. the rats of HHP group weregiven with oxpentifylline (PTX50mg/kg)by peritoneal injection 12 hoursbefore and after contrast media injection. At the same time, equal volumof normal saline (10ml/Kg) was injected through tail vein in rats from NNand HN. 48 hours after contrast media injection, the rats were executedand blood samples were prepared to determine total cholesterol,triglyceride, serum creatinine, creatinine clearance(Ccr), fractionalexcretion of sodium and potassium, and AngtensionⅡ(AngⅡ) concentration. The histologic change of kidney tissue was examined bylight microscope(HE staining, TUNEL staining). The expression of NFκBin the renal tissue was detected using immunohistochemical method.RESULTS:1. An increase of cholesterol was observed in all rats with highcholesterol diet. There was no obvious difference among all six groups.2. Scr and FeNa~+ of rats in HH, HL and HI groups were obviouslyhigher than those in HHP, HN and NN groups. Scr and FeNa~+ of rats inHH grous were obviously higher than those in HL and HI groups, whileno pronouced differece was discoved between HL and HI group. Ccr ofrats in HH, HL and HI groups were obviously lower than those in HHP,HN and NN groups. Ccr of rats in HH grous was obviously lower thanthat in HL and HI groups, while no pronouced differece was discovedbetween HL and HI group. FeK~+ of rats in HL, HI and HH groups wasobviously increased.3. There was pronouced increase of serum AgⅡlevel in all RCMinjected rats, and the increase in HH group was the most obvious.4. Renal pathology4.1 HE staining:No obvious change was obseved In the kidney of normal rats. In therats injected diatrizoate tubular nerosis, tubular epethelial vaculoe andprotein-cell-cast were found. There were tubular epethelial edema,vaculoe and nuclear condensation with various degrees in rats injectedwith LOCM or IOCM. However, only mild tubular epethelial edema wasdiscovered in HN and HHP groups.4.2 TUNEL stainingPercentage of apoptotic cells in HH group was higher than all othergroups, and obvious renal cell apoptosis were observed 4.3 Immunohistochemistry staining The express of NFκB was mainly observed in endothelial cells ofcapillary loops.The average gray value of positive cells in HH groupdecreased(P＜0.01).Conclusion:1. Nephrotoxicity induced by HOCM increased in the rats withhypercholesterolemia. However, there was no obvious difference betweenIOCM group and LOCM group.2.PTX has protective effects on HOCM induced RCN in theenvironment of hypercholesterolemia.3. AgⅡ,NFκB may play a role in RCN.
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