The Preventive Effect And Mechanism Of Prostagnin E1 On Contrast-induced Acute Kidney Injury

Part one The preventive effect of prostaglandin E1 on contrast-induced acute kidney injury after percutaneous coronary interventionObjective: The aim of this study is to explore the effect and mechanism of prostaglandin E1 on CIAKI after percutaneous coronary intervention through multicenter,prospective and randomized controlled trial.Method: A total of 641 patients with coronary heart disease who underwent percutaneous coronary intervention(PCI)in Tianjin chest hospital,tianjin first center hospital,teda international cardiovascular hospital,tianjin fourth central hospital.from January 2015 to December 2017 were enrolled consecutively.The patients were randomly divided into prostaglandin E1 group and control group,all selected patients were given hydration therapy.Prostaglandin E1 group giving prostaglandin 20ug/ days and hydration treatment,the control group only treated with water treatment.The levels of BUN,Scr,Ccr,Cys-C,SOD,GSH,CRP of all patients before and 48 h,72h after PCI were recorded.The level of change;the primary end point was the incidence of CIAKI,defined as scr increased over 44.2umol/l or more than 25% compared to the baseline 48~72h after contrast exposure,and the main adverse events occurred during hospitalization.Results: 1.There was no statistical difference in baseline data between the two groups(P<0.05)2.The incidence of CIAKI in Prostaglandin E1 group was obviously lower than that in the control group(4.0% vs10.9%).Multivariate logistic regression analysis showed that prostaglandin E1 was a protective factor of CIN(OR=0.342,95% CI: 0.174--0.672,P = 0.002).3.There was statistically significant in the prostaglandin E1 group and the control group,between the low-risk stratification group and the medium-risk stratified population(the ?2 was 6.798 and 5.486,both P<0.05).4.The baseline levels of blood tests of BUN,Scr,Ccr,Cys-C,SOD,GSH and CRP before PCI in the two groups were not statistically significant(P>0.05).5.in the prostaglandin E1 group and the control group,the levels of Ccr,Cys-C and CPR increased compared to baseline 48 h,72h after PCI,and SOD and GSH levels decreased compared to baseline 48 h,72h after PCI,(P<0.05)6.48 h after PCI,the levels of Cys-C and CRP were lower in the prostaglandin E1 group than those in the control group(P<0.05).7.72 h after PCI,CRP in prostaglandin E1 group was lower than that in control group,Ccr,SOD and GSH in prostaglandin E1 group were higher than those in control group,the difference was statistically significant(P<0.05).8.There was no significant difference between the two groups in the occurrence of major adverse events(2.2%vs2.8%,P=0.624).Conclusion: 1.Prostaglandin E1 can effectively reduce the incidence of CIAKI after percutaneous coronary intervention.2.Prostaglandin E1 may be effective in reducing the risk stratification of CIAKI for low-risk and medium-risk groups,while the occurrence of CIAKI in high-risk and high-risk groups may be ineffective.3.Prostaglandin E1 may reduce the occurrence of CIAKI mainly by dilating renal vessels,anti-inflammation and anti-oxidative stress.Part two The relieve effect and mechanism of Prostaglandin E1 on contrast-induced acute kidney injury in ratsObjective: To explore the protective effect and protective mechanism of prostaglandin E1 on CIAKI by establishing a rat model of contrast-induced acute kidney.Methods: 45 healthy Wistar rats were randomly divided into 3 groups: the control group(group A),the CIAKI model group(group B)and the prostaglandin E1 group(group C),each group was 15.The levels of Scr,CRP,TNF alpha and IL-6 were detected before and 24 h and 48 h after the experiment.The levels of MAD,SOD,NO and the expression of Bcl-2 and protein in kidneys were detected after injection of contrast medium 48 h,and the morphological changes of kidneys were observed under light and electron microscope.Results: 1.(1)there was no statistically significant difference in serum Scr level before the injection of contrast agent(P>0.055).(2)the Scr level of group B and group C raised compared to baseline(p<0.05).However,the Scr level of group C and group A was lower compared to group B(p<0.05).(3)the Scr level of group B and group C was still higher compared to baseline(p<0.05)72h after injection of contrast agent.However,Scr level in group C was lower than that in group B(p<0.05).2.(1)there was no statistically significant difference in the levels of CRP,TNF-? and IL-6 in the three groups.(2)24h and 48 h after the injection of contrast agent,the levels of CRP,TNF-? and IL-6 in group B and group C were higher compared to baseline(p<0.05).(3)24h and 48 h after injection of contrast agent,the levels of CRP,TNF-? and IL-6 werel lower than group B(p<0.05).3.48 h after injection of contrast agent,(1)MDA level in group C and group B was higher than that in group A,and MDA level in group C was lower than group B(p<0.05);(2)SOD and NO level in group C and group B were lower than group A,and SOD and NO level of group C was higher than group B(p<0.05).4.48 h after injection of contrast agent,(1)the expression of Bax protein in group C and group B increased significantly higher than that in group A(P < 0.05),and the expression of Bax protein in group C was lower than that in group B(P < 0.05).(2)the expression of bcl-2 protein in group C and group B was lower than that of group A(P < 0.05).The expression of Bax protein in group C was higher than that in group B(P < 0.05).5.Morphological changes of the kidney under the light microscope :(1)the renal tubules and glomeruli in the control group were basically normal;(2)the renal tubules and renal interstitium in CIAKI group showed a large number of inflammatory cell infiltration,severe swelling of the renal tubular epithelial cells,vacuolar changes,large number of tubular types in the lumen,and even occlusion.(3)the prostaglandin E1 group of renal tubules and renal interstitium had only a small amount of inflammatory cell infiltration,and the renal tubular epithelial cells were slightly swollen,and a small number of tubular cells were seen in the lumen.6.Morphological changes of the kidney under the electron microscope(1)the control group of renal tubules and glomerulus ultrastructure were basically normal;(2)severe thickening of the basal membrane of the renal tubule in the CIAKI group,swelling of the endoplasmic reticulum,severe swelling of mitochondria in endothelial cells,disorder of the border crest,and even disappeared;(3)the basal membrane of the renal tubules of the prostatin E1 group was mildly thickened,the mitochondria in the endothelial cells were mildly swollen,and the ridge arrangement was roughly normal,and the microvilli of the lumen were more complete.Conclusion: 1.The occurrence of CIAKI in rats may be related to the effect of contrast agent induced renal blood contraction,oxidative stress injury,inflammatory reaction injury,and apoptosis.2,prostaglandin E1 may alleviate renal injury in rats induced by reducing renal vasoconstriction caused by contrast agents,antioxidative stress injury,anti inflammation,and antiapoptosis.