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The Effect Of Sacubatril/valsartan On The Expression Of Autophagy-related Genes Beclin-1 And LC3 In Myocardial Ischemia/reperfusion Injury

Posted on:2022-03-06Degree:MasterType:Thesis
Country:ChinaCandidate:L R ZhuFull Text:PDF
GTID:2504306320451654Subject:Internal Medicine
Abstract/Summary:
Destination In this study,the model of myocardial ischemia/reperfusion injury was established by ligating the left anterior descending branch of the rat.Observe the expression of autophagy protein Beclin-1 and LC3 in myocardial ischemia-reperfusion injury.Explore the role of autophagy in myocardial ischemia reperfusion injury.On this basis,to explore the regulation of Nuoxinto on myocardial ischemia-reperfusion injury and autophagy injury.Methods There are 72 male rats were randomly divided into Sham operation(Sham)group,myocardial Ischemia/Reperfusion(I/R)group,myocardial Ischemia/Reperfusion+ Sacubitril/Valsartan(I/R+ Entresto)group,24 in each group.8 rats in each group were executed at different time,in immediately,4 weeks,and 8 weeks.The rat left ventricular anterior wall myocardium of each group was taken to assess the morphological changes by HE staining.The expression levels of Beclin-1 and LC3 in the myocardial tissues of each group were explored by real-time quantitative PCR and Western blotting.Compare the changes of indicators within,between groups,and in each time phase,analyzing whether they are statistical significant with statistical methods.Results1.Changes in myocardial tissue of rats morphology.In the Sham group,the myocardial cells were evenly stained,the cells arranged in rows without swelling.The fibers were intact,and the inflammatory cell infiltration was not obvious.The myocardial tissue injury of the rats in the I/R group was more obvious in the 4th week than the immediate samples,and the 8th week was better than the 4th week.The morphological changes of the myocardial tissue in the I/R+Entresto group in the 4th week were better than those obtained immediately,and the8 th week was better than the 4th week.2.Beclin-1 and LC3 m RNA levels and protein expression levels in myocardial tissues of rats in each group.Intra-group comparison: There was no significant difference in Sham group between immediately,4th week and 8th week.The expression levels of Beclin-1 and LC3 m RNA and protein in the 4th week in I/R group were higher than those obtained immediately and the 8th week(P<0.05),with a time-effect,which means that the expression levels of Beclin-1 and LC3 m RNA and protein in the 4th week were highest,and there was no significant difference between immediately and the 8th week(P>0.05).The expression levels of Beclin-1 and LC3 m RNA and protein in the4 th week in I/R+ Entresto group were higher than those obtained immediately and the8 th week(P<0.05),and the 8th week was lower than immediately(P<0.05),with a time-effect too,which means that the expression levels of Beclin-1 and LC3 m RNA and protein in the 4th week were highest.Comparison between groups: Compared with sham group,the expression levels of Beclin-1 and LC3 m RNA and protein in each time phase of I/R group were higher than those in sham group(P < 0.05).In group I/R+ Entresto,the expression levels of Beclin-1 and LC3 m RNA and protein in immediately and the 4th week time phase were higher than those in group sham(P<0.05),but there was no significant statistical difference was found in the 8th week between group I/R+ Entresto and group sham.Group I/R+ Entresto compared to group I/R,no significant statistical difference was found in immediately time phase.Both the express levels of Beclin-1 and LC3 m RNA and protein of 4th week and 8th week in group I/R+ Entresto were lower than which in group I/R(P<0.05).Conclusion This study is based on the verification that Nuoxinto protects myocardial ischemia-reperfusion injury,finding that Nuoxinto can reduce the excessive activation of autophagosomes during ischemia-reperfusion to reduce the damage caused by myocardial ischemia-reperfusion to myocardial tissue.And its mechanism may be related to the repair of autophagic flux.In summary,Nuoxinto may protect the myocardium after ischemia-reperfusion injury by repairing autophagic flow,and it has a certain time effect.
Keywords/Search Tags:Sacubitril/Valsartan(Entresto), myocardial ischemia-reperfusion injury, autophagy, Beclin-1, LC3
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