Protective Effect And Mechanism Of Alprostadil Injection On Contrast-induced Nephropathy In Rats

Objective: To observe the protective effect and mechanisms of alprostadil injection oncontrast-induced nephropathy in rats, in order to provide experimental evidence of alprostadilinjection in prevention of contrast-induced nephropathy after PCI.Methods:120male and female Wistar rats were randomly divided into six groups andeach group has20rats. The rats were feed in metabolic cages. After24hours water deprivation,all the groups were given25%glycerol injection by intramuscular injection except the controlgroup. The control group was given sodium chloride injection. After24h of glycerol injection,alprostadil (5,10,20μg/kg) and reduced glutathione (600mg/kg) for injection wereadministrated by intravenous injection daily for3days. After1h of the first alprostadilinjection, contrast medium was injected slowly through caudal vein. All rats were sacrificed onday4after1h of last injection of alprostadil. Renal function parameters, oxidative stressmarkers (MDA, SOD, GSH-Px). AngII, PGI2and TXA2levels were measured.Histopathological fundings and Transmission Electron Microscopy fundings of kidney weremeasured.Results:①The model group had higher BUN and SCr (P<0.01or P<0.001) content aswell as lower CCr (P<0.01) compared to control group; The glutathione600mg/kg group andthe alprostadil10、20μg/kg groups had higher CCr (P<0.05or P<0.01) as well as lower Scr andBUN content (P<0.05or P<0.01) compared to model group.②In model group, the AngII andTXA2content were significantly higher (P<0.01or P<0.001), and the PGI2content andPGI2/TXA2ratio were lower (P<0.01or P<0.001) compared to control group;In glutathione600mg/kg group and alprostadil10、20μg/kg groups, the AngII and TXA2contents weresignificantly lower (P<0.05or P<0.01), and the PGI2content and PGI2/TXA2ratio were higher(P<0.05~P<0.001).③The model group had higher24h and48h UP content as well as lowerUCr and UA (P<0.001) compared to control group; The glutathione600mg/kg group and thealprostadil20μg/kg group had higher24h and48h UCr and UA content as well as lower UP content (P<0.05or P<0.01) compared to model group.④In model group, the SOD andGSH-Px activities were significantly lower, and the MDA content was higher (P<0.01)compared to control group; In glutathione600mg/kg group and alprostadil10、20μg/kg groups,the SOD and GSH-Px activities were significantly higher, and the MDA content was lower(P<0.05or P<0.01).⑤The mean scores of tubular vacuolation and proteinaceous casts werealso significantly lower in glutathione600mg/kg group and alprostadil20μg/kg groupscompared to model group.Conclusion: These results demonstrated the renoprotective effect of alprostadil againstCIN through modulation of oxidative stress and renal blood flow.