| Obective:To investigate the effects of defroxamne on myocardial cells in diabetic rats,to evaluate the effect of deferoxamine on myocrdial protection induced by sevoflurane postconditioning in diabetic rats,to provide a new target and theoretical basis for myocardial protention indiabetic patients.Merhods:(1)24 male SD rats weigbing 240?290g were Tandomly.divided into 3 groups(n=8 each):normal group(group N),diabetic group(group D),Deferoxamine conditioning group(group C).Group N was continnously feeded by normal foclder for 4 weeks;group D was induced via intraperitoneal injection of streptozotocin(STZ)55mg/kg and feeded by normal fodder for 4 weeks;group C was induced by injection of streptozotocin(STZ)55mg/kg and DFO 0.2mg·g-1·d-1 during the forth week.The water consumption of 24hours,the weight and blood glucose were monitored in rats at first,third,tenth,seventeenth;twenty seventh and thirty first days.The heart of the rats were sacrifgiced at 31st day,While the blond was taken for test of cTnI.The pathological changes were cbserved by HE staining and Prussian blue staining.Western-blot was used to determine the expression of microtubule-associated Protein 3 ?(LC3?),ferritin heavy chain(FTH)and nuclear receptor coactivator 4(NCOA4).(2)40 male SD rats wdighing 240?290g were randomly doviced into 5 groups(n=8 each):sham operation group(group Sham),ischemia and reperfusion group(group IR),ischemia and reperfusion+sevoflurane postconditioning group(group IR+SEVO),ischemia and reperfusion+Deferoxamine group(group IR+DFO),and ischiemia and reperfusion+Deferoxamine+sevoflurance postconditioning group(group IR/DFO+SEVO).Group Sham was continuously perfused for 150min.Group IR was given the ischemia for 30min and reperfusion for 120min.Group IR+SEVO was given 2.5%sevoflurance for 15min at the begining of the reperfusion.Group IR+DFO was given DFO0.2mg·g-1·d-1 before ischemia and reperfusion for a week.Group IR+SEVO+DF was given DFO0.2mg·g-1·d-1 for a week and given 2-5%sevoflurane for 15min the begining of the reperfusion.During the I/R injury,Heart rate,mean arterial pressure were measured to evaluate the cardiac function After inducing the I/R injury,the following parameters were measured:rnyocardial infarc size,Pathological changes on myocardium and pxotein eapression of chronic Troponin I(cTnI),microtubule associated protein 1 light chain 3-?,,AP1LC3-?,(LC3 ?),ferritin heavy chain(FTH)and Nuclear receptor coactivator 4(NCOA4).Results:(1)In the group D and the groupC,blood glucose level increased to 16.6mmol/l at the 3rd day,blood glucose in daytime was higher than 16.6mmol/l at tenth,seventeenth,twenty seventh and thirty first days.Compared with Sham group,the difference of blood glucose is statistically significant.Pathological sections showed that the myocardial structure of group N was clear and orderly,the cell morphology was normal,Prussian staining showed that there were a small amount of iron containing granules in the myocardial cells;group D myocardial fibers were basically orderly arranged,the cells were slightly edermetous,prussian staining showed that the number of iron containing granules in the myocardial cells was more than that in the group N;myocardial fibers in group C were basically orderly arranged,the cell morphology was basically normal,prussian staining showed that the iron content was similar to that of group N.Compared with group N,the expression of myocardial cTnI?FTH?NCOA4 and LC3? were significantly up-regulated in the grpup D;Gompared with group D,the expression of myocardial cTnI,FTH,NCOA4 and LC3?were down-regulated it the group C.(2)compared with group Sham the expression of myocardial cTnI and myocardial infarct size were significantly np-regulated in the other four grtoups to cardiac function,the statistics of group IR+DFO+SEVO at the end of reperfusion gets better than that of group IR+SEVO(P<0.05).Compared with group IR.myocardial infarct size and the expression of cTnI,FTH and NCOA4 were significantly down-regulated in group IR+DFO and group IR+DF-SEVO(P<0.05).Conclusion:(1)There was no significant effect on blood glucose level and uirne volume of diabetie rats,and the autophagy level of ferritin in myocardial cells was decreased when the treatment of deferoxamine for a week.(2)The sevoflurane post-treatmet had no effect on the autophagy pathway of ferritin in rats' cardiomyocytes.(3)Reducing iron content with derferoxamine in diabetic rats can improved the myocardial protective effect of sevoflurane post-treatment in diabetic rats. |
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