Dexmedetomidine protects myocardium from ischemia/reperfusion injury by down regulating expression of Dectin-1 and inhibiting immune cells infiltration
Objective:To explore the molecular mechanism of dexmedetomidine(Dex)protecting ischemia/reperfusion(I/R)myocardium.Methods:Wild type mice were grouped into control(Control)group,sham operation(Sham)group,WT I/R group,WT Dex group,and Dectin-1 knock out mice were grouped into KO I/R group and KO Dex group in the in vivo study(n=6).TTC stain-ing was used to determine the myocardial infarction area(%)of the above six groups of mice.HE staining and pathological analyze was used to determine the myocardial injury.Serum TNF-α,IL-6 and IL-10 levels in mice were detected by ELISA.Flow cytometry(FCM)was used to count and sort of infiltrating M2 macrophages and neutrophils in myocardium.qPCR assay was used to determine the Dectin-1 mRNA expression in the above sorted cells.Results:TTC results showed that there was no myocardial infarction in the mice of Control group and Sham group.Compared with the WT I/R group,the infarct volume was significantly lower in WT Dex group,KO I/R group and KO Dex group(P<0.05).Compared with the KO I/R group,the infarct volume was reduced in KO Dex group(P<0.05).The results of HE staining showed that the myocardial fibers of the WT I/R group of mice were disorderly arranged,with a large number of broken myocardial fibers,while the myocardial fibers of the WT Dex group,KO I/R group and KO Dex group of mice had a little breakage,the structural damage was not significant,and the myocardial arrangement was relatively neat.The degree of myocardi-al injury of mice in KO Dex group were less than that in KO I/R group mice.ELISA results showed that compared with Sham group,the serum TNF-α and IL-6 levels of the mice in WT I/R group were significantly increased,and the IL-10 level was significantly de-creased.Compared with WT I/R group,serum TNF-α and IL-6 levels of the mice in WT Dex group and KO I/R group were significant-ly decreased,and IL-10 level was significantly increased.Compared with KO I/R group,the serum TNF-α and IL-6 levels of the mice in KO Dex group were significantly decreased,and the IL-10 level was significantly increased(P<0.05).FCM cell counting results showed that compared with Sham group,a large number of M2 macrophages and neutrophils were infiltrated in the myocardium of WT I/R group of mice(P<0.05).Compared with WT I/R group,the M2 macrophages and neutrophils infiltrated in the myocardium were significantly decreased in WT Dex group,KO I/R group and KO Dex group of mice(P<0.05).While there was no significant differ-ence between the KO I/R group and the KO Dex group mice(P>0.05).qPCR results showed that compared with Sham group,the ex-pression level of Dectin-1 mRNA in the myocardial infiltrated M2 macrophages and neutrophils were significantly up-regulated in WT I/R group of mice(P<0.05).While compared with WT I/R group,the expression level of Dectin-1 mRNA in Dex group of mice was sig-nificantly lower(P<0.05).Mice in KO I/R group and KO Dex group did not express Dectin-1.Conclusion:The protective mecha-nisms of Dex preconditioning on I/R injured myocardium involves reducing the infiltrating number of M2 macrophages and neutrophils in myocardium after I/R injury,which may be achieved by inhibiting the expression of Dectin-1.
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