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Protective Mechanism Of Deferoxamine On Myocardial Ischemia-reperfusion Injury In Diabetic Rats

Posted on:2024-01-12Degree:MasterType:Thesis
Country:ChinaCandidate:Y ChenFull Text:PDF
GTID:2544307085476494Subject:Anesthesiology
Abstract/Summary:PDF Full Text Request
Objective:To investigate the relationship between deferriamine(DFO)and hypoxia inducer-1αin the myocardial protection after sevoflurane treatment and the regulation of mitochondrial respiratory function.Methods:The hearts of 80 GK rats(SPF-level male non-insulin-dependent non-obese spontaneous type II.diabetic rats)were prepared by the Langendorff method for successful perfusion of an ex vivo model,and divided into 5groups according to the random number table sequence,each group of 16 animals:control group(C),ischemia-reperfusion group(I/R),sevoflurane post-treatment group(SPostC),the sevoflurane post-treatment group was pretreated with deferoxamine(DFO+SPostC),the sevoflurane post-treatment group was given a deferoxamine and HIF-1αinhibitor(DFO+SPostC+2ME2).The following indicators were measured and collected at the end of reperfusion:mitochondrial respiratory function(mitochondrial 3-state and 4-state respiration and respiratory control rate),mitochondrial respiratory enzyme activity,mitochondrial ultrastructure,and the level of HIF-1αprotein expression via Western blot.Results:The differences between the five groups were statistically significant(FState3=105.82,FRCR=341.28,FNADHO=277.45,FSUCO=263.35,FCcO=340.42,FHIF-1α=2313.92),compared with Group C,the significant differences in respiratory function and enzyme activity parameters in the remaining groups were presented(P<0.05),and the expression of HIF-1αin the DFO+SPostC group was significantly increased when compared with the I/R group(P<0.05),the expression of mitochondrial III-state respiration(State3),respiratory control rate(RCR),nicotinamide adenine dinucleotide oxidase(NADHO),cytochrome C oxidase(CcO)and succinate oxidase(SUCO)increased significantly,but HIF-1αexpression was inhibited in the DFO+SPostC+2ME2 group,and there was no significant change in other indexes(P<0.05).Conclusion:Deferramide can up-regulate HIF-1αlevel,thereby restoring mitochondrial respiratory function and mitochondrial enzyme activity,which may be the key point in alleviating myocardial ischemia reperfusion injury in diabetic rats after sevoflurane treatment.
Keywords/Search Tags:Sevoflurane, Myocardial ischemia-reperfusion injury, Hypoxia-inducible factor-1, Mitochondrial respiratory function
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