The Study On MicroRNA-1 And Kir2.1 Levels In Ventricular Myocardial Tissue Of Mice With Coxsackie Virus B-induced Myocarditis

Objective To investigate the level changes of pri-miRNA-1,dicerlmRNA,kcnj2mRNA and potassium channel Kir2.1 protein in ventricular myocardial tissue of viral myocarditis mice infected by coxsackievirus B;and to elucidate the significance of these changes.Methods 140 four-week-old male Balb/c mice were divided randomly into a VMC group(n=80) and the control group(n=60).Mice in the VMC group were assigned to one of the four subsets:7 day(n=20),14 day(n=20),28 day(n=20) and 42 day(n=20).Mice in the control group were assigned similarly(n=15). 0.1ml CVB3 Nancy suspension was injected intraperitoneally into each mouse in the VMC group.0.1 ml RPMI1640 medium was used as control.Levels of pri-miRNA-1,dicer1 mRNA and kcnj2 mRNA were determined using RT-PCR. Level of potassium channel Kir2.1 protein were determined with immunohistochemistry.Results(1) Inflammatory cell infiltration or myocardial cell necrosis were exhibited in ventricular myocardial tissue of the mice in the VMC group.(2) Compared to the control group,expression levels of pri-miRNA-1 and dicer1 mRNA in ventricular myocardial tissue of the mice in the VMC group were significantly elevated(P＜0.01),with peak on day 14.(3) The expression level of kcnj2 mRNA in ventricular myocardial tissue of the mice in the VMC group was significantly reduced compared to that of the control group(P＜0.01),and the lowest was observed on day 14.(4) compared with control group Kir2.1 in ventricular myocardial tissue of VMC group mice was significantly reduced(P＜0.01) and its level was reduced more and more lower from 7 day.(5) In the VMC group,the expression levels of pri-miRNA-1 and dicer1mRNA were positively correlated(r=0.462,P＜0.01).(6) In the VMC group,The expression level of pri-miRNA-1 was negatively correlated with that of kcnj2mRNA (r=-0.261,P＜0.05) and kir2.1 protein(r=-0.161,P＜0.05).Conclusion miRNA-1 is up-regulated while the kcnj2mRNA and the kir2.1 are down-regulated in ventricular myocardial tissue of viral myocarditis mice. The up-regulation of miRNA-1 might be responsible for the reduced expression of Kir2.1 protein by regulating transcription of the kcni2 gene.