The Effects of Dexmedetomidine on Autophagy in Myocardial Tissues of Rats with Myocardial Ischemia-reperfusion and SIRT1/mTOR Pathway Proteins
Objective:To explore the efftects of dexmedetomidine on autophagy in myocardial tissues of myocardial ischemia-reperfusion rats and NAD dependent deacetylase(SIRT1)/rapamycin target protein(mTOR)pathway proteins.Methods:45 SPF grade male SD rats of 8 weeks old(mean weight 220 g)were randomly divided into sham-surgery group,model group,and dexmedetomidine group,with 15 rats in each group;the model group and dexmedetomidine group were used to replicate myocardial ischemia-reperfusion model.The dexmedetomidine group was infused with dexmedetomidine hydrochloride injection before modeling,while the other two groups were infused with equal amount of physiological saline.Serum myocardial injury markers creatine kinase isoenzyme(CK-MB)and troponin Ⅰ(cTnⅠ),inflammatory factors interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were detected before and 24 hours after reperfusion;after euthanizing rats,TTC staining was used to calculate the percentage of myocardial infarction area.qRT-PCR and Western blot were used to detect autophagy related proteins microtubule associated protein 1A/1B light chain 3(LC3)Ⅱ/Ⅰ,beclin-1,and P62 proteins,SIRT1 and mTOR,too.Results:CK-MB,cTnⅠ,IL-6,and TNF-α levels in the model group.and dexmedetomidine group before reperfusion were significantly higher than sham-surgery group,and the dexmedetomidine group was lower than model group(P＜0.05);CK-MB,cTnⅠ,IL-6,and TNF-α levels in the model group after reperfusion were higher than before reperfusion,while the dexmedetomidine group was lower than before reperfusion,what's more,the dexmedetomidine group was significantly lower than model group(P＜0.05).The percentage of myocardial infarction area,expression levels of LC3 Ⅱ/Ⅰ,beclin-1 and P62 proteins,SIRT1 and mTOR in the model group and dexmedetomidine group were higher than those in the sham-surgery group,but the dexmedetomidine group was significantly lower than the model group(P＜0.05).Conclusion:Myocardial ischemia-reperfusion may furtherly increase myocardial injury and inflammatory response.Pretreatment with dexmedetomidine can partially alleviate myocardial injury,inflammatory response,myocardial infarction,and autophagy,which may be related to the inhibition of SIRT1/mTOR signaling pathway activity.
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