Research Of Atorvastatin Protect Against Contrast-induced Nephropathy By Inducing Heme Oxygenase-1Expression

Objective: To detect whether atorvastatin can induce the expression ofheme oxygenase-1(HO-1) in rat kidney,and to explore the protective effects ofatorvastatin in contrast-induced Nephropathy(CIN) and the possible mediated byHO-1echanisms. Methods:33clean healthy male SD (Sprague-Dawley) rats(weight about350g) were divided randomly into4groups: control group (n=6),model group (n=9), atorvastatin group (n=9), and Zinc protoporphyrin IX group(Zinc protoporphyrin IX, ZnPPIX)(n=9). The experiment steps are as follows:all the rats were intramuscular injected gentamicin80mg/kg for2days (2times/day) and fed with ordinary food but forbidden drink24hours on the thirdday. then the rats in each group were given different processing methods:ZnPPIX group was given atorvastatin (30mg/kg) via gastric lavage andZnPPIX(7.5mg/kg) via intraperitoneal injection,Atorvastatin group was givenatorvastatin (30mg/kg) via gastric lavageand and equivalent nomal saline viaintraperitoneal injection, Control group and model group were given equivalentnomal saline via gastric lavage and intraperitoneal injection.12hours later,Atorvastatin group and ZnPPIX group were given another dose of atorvastatin(30mg/kg) via gastric lavage, while the control group and model group weregiven equivalent nomal saline. On the fourth day, before intravenous injectingpan shadow meglumine,among the model group, atorvastatin group andZnPPIX group, three rats in each group were killed chosen randomly to put to death to detecte the expression and distribution of HO-1protein in kidney bywestern blotting and immunohistochemical. All the remaining rats wereexsanguinated through caudal vein to check the creatinine(Cr) and ureanitrogen(BUN). At the same time, rats in model group, atorvastatin group andZnPPIX group were injected76%pan shadow meglumine (10mL/kg) viacaudal vein, and the control group were injected equivalent nomal saline. Thenall rats were forbidden drinking for24hours and killed after72hours. Bloodsample was obtained through inferior vena cava to check the Cr,BUN.Theconcentration of Interleukin-6(IL-6), monocyte chemotactic protein-1(MCP-1), Malondialdehyde (MDA) and Total Antioxidant Capacity (T-AOC)in supernatant of renal homogenate were detected. HE dyeing was used toobserve the structure changes of the kidney and immunohistochemical was usedto observe the changes of Bax, Bcl-2and apoptosis Index in the renal tissue.Results:1. The CIN model of rats was successfully established. The renalfunction of rats in control group showed no obvious difference between nomalsaline intravenous injecting before and72hours later. But in model group, therat renal function parameters increased obviously in72hours later of genericshadow meglumine injecting than injecting befor, which is accord with the CINdefinition of2011Europe urogenital radiation association guidelines: In case ofruling out other causes. There is renal injury in48-72hours after injectingcontrast medium (the level of serum Cr increase by25%compared to the basallevels or absolute value elevate44.2umol/L before applicating it).2. There were obvious differences in HO-1protein expression among model group,atorvastatin group and ZnPPIX group. When compared with model group, theexpression levels of HO-1increased significantly in Atorvastatin group, butdecreased obviously in ZnPPIX group.3. The BUN,Cr,IL-6,MCP-1,MDA,TAOC,Bax,Bcl-2and AI are significant different among each group. Comparedwith control group, the BUN,Cr,IL-6,MCP-1,MDA,Bax,Bcl-2and AI in Modelgroup,Atorvastatin group and ZnPPIX group increased significantly,whileTAOC decreased obviously. When compared with model group, the BUN, Cr,IL-6, MCP-1, MDA, Bax and AI in atorvastatin group are significant lowerwhile the Bcl-2, Bcl-2/Bax and TAOC are significant higher. The BUN, Cr,IL-6, MCP-1, MDA, Bax and AI in ZnPPIX group are significant higher, whilethe Bcl-2, Bcl-2/Bax and TAOC are significant lower. Conclusions：1.The ratCIN model could be successfully established by intramuscular injectiongentamicin+intravenous injection76%generic shadow meglumine.2.Atorvastatin could induce the HO-1protein expression in rat kidney,which canbe blocked by ZnPPlX.3. The atorvastatin could prevent against CIN and thisrol is probably mediated by inducing HO-1expression.4. Anti-inflammation,anti-oxidative stress and inhibitting cell apoptosis might be the major renalprotecting mechanisms of HO-1．...