The Protection Mechanism Of Atorvastatin On Contrast-induced Acute Kidney Injury In Rats

Objective:The present study was designed to investigate the protective effect ofatorvastatin on contrast-induced acute kidney injury(CI-AKI) in rats，and to explorethe protection mechanisms of atorvastatin on contrast-induced acute kidney injury inrats.Methods:(1)Sixty SD rats were randomly divided into five groups,including normalcontrol group(NS group),contrast media control group(CM group),small doseatorvastatin group(SDA group),high dose atorvastatin group(HDA group),load dosageatorvastatin group(LDA group):rats in the SDA group,HDA group and LDA groupreceived atorvastatin1mg/kg/d,8mg/kg/d,8mg/kg/d,respectively,and rats in the LDAgroup received atorvastatin8mg/kg1hour before injected contrast media,rats in theNS group and CM group received equivalent normal saline(NS).(2) Low-osmolarcontrast media was injected by caudal veins of all rats except the rats in NS group at10ml/kg,while equivalent NS was injected in the NS group. Samples were obtained atthe24hour and72hour after injection contrast media.(3)The pathologicalmorphology of renal was observed under microscopy.(4)The level of Scr and Cys-Cin serum was detected by automatic biochemistry analyzer. The level ofmALB,NAG,α1-MG in urine was detected by ELISA method.(5) The level of hsCRPin serum was detected by ELISA method,while the activity of SOD in kidney tissuewas detected by the method of xanthine oxidase.(6)Localization and expression ofeNOS protein and Na~+,K~＋-ATPase activity in kidney tissue were detected byimmunohistochemistry staining method.Results:(1) The level of Scr，Cys-C， mALB，NAG and α1-MG was increased ingroups which injected contrast media than NS group,and the above indicators alldecrased in groups treatment with atorvastatin than CM group(p＜0.05), and therewas no significant difference between HDA and LAD group(p＞0.05); in CM group， each indicator was higher at72hour than24hour(p＜0.05)，while there was nosignificant difference in other groups(p＞0.05).(2) The level of hsCRP in serum wasincreased in groups which injected contrast media than NS group,and the level ofhsCRP in serum was significant decreased in groups treatment with atorvastatin thanCM group(p＜0.01). The level of hsCRP in serum was higher at72hour than24hourin CM group(p＜0.05)，while the level of hsCRP in serum was lower at72hour than24hour in LDA group(p＜0.05)，and there was no significant difference betweenHDA and LAD group(p＞0.05).(3) The activity of SOD was decreased in groupswhich injected contrast media than NS group(p＜0.01).To compare CM group，theactivity of SOD was significant increased in groups treatment with atorvastatin (p＜0.01). The activity of SOD was lower at72hour than24hour in CM group(p＜0.05)，while the activity of SOD was higher at72hour than24hour in LDA group(p＜0.05),and there was no significant difference in HDA and LAD group(p＞0.05).(4) Theexpression of eNOS and Na＋,K~＋-ATPase protein both decreased in groups whichinjected contrast media than NS group(p＜0.01).The expression of eNOS and Na＋,K＋-ATPase protein both increased in groups treatment with atorvastatin than CMgroup(p＜0.05)，there was no significant difference between SDA and HAD group at24hour after injected contrast media(p＞0.05). In groups treatment with atorvastatin，the expression of eNOS and Na＋,K~＋-ATPase protein both increased in72hourgroup than24hour group(p＜0.05)， except the expression of eNOS was nosignificant different in SDA group and LDA group in24hour group between72hourgroup，while in CM group，the expression of eNOS and Na＋,K~＋-ATPase proteinboth decreased in72hour group than24hour group(p＜0.05).Conclusion:Application short-term atorvastatin have a protective effect oncontrast-induced acute kidney injury in rats,the effection may be through improveendothelial function,anti-inflammation,oxidative stress and improve Na~+, K~+-ATPase activity to realize,and this effection has no obvious relation to dose,andgive load dose before injection contrast media can further reduce the acute kidneyinjury.