Protective Effect and Mechanism of Down-regulation of miR-223 Expression on Myocardium of Septic Cardiomyopathy Mice
Objective:Investigating the protective effect and mechanisms of downregulating miR-223 expression on the myocardium of mice with septic cardiomyopathy(SCM).Methods:Using a random number table,27 male SPF C57BL/6 mice aged 8-10 weeks were allocated into different groups:SCM model groups at different time points(0 h,6 h,12 h,18 h,24 h),Normal group,SCM group,miR-223 antagomir NC group,and miR-223 antagomir group,with 3 mice in each group.The SCM mouse model was established by intraperitoneal injection of lipopolysaccharide(LPS)at a dose of 15 mg/kg.The miR-223 antagomir NC group and miR-223 antagomir group received consecutive tail vein injections of miR-223 antagomir NC and miR-223 antagomir,respectively,for 3 days before modeling.Reverse transcription-polymerase chain reaction(RT-PCR)was used to study the expression of miR-223 in the myocardial tissue of mice in different time point groups of the SCM model.Hematoxylin-eosin(HE)staining was performed to observe the myocardial pathological changes in the Normal group,SCM group,miR-223 antagomir NC group,and miR-223 antagomir group.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of cTnⅠ,BNP,CK-MB,IL-6,IL-1β,and TNF-α in mouse serum in the Normal group,SCM group,miR-223 antagomir NC group,and miR-223 antagomir group,and correlation analysis was conducted.Results:In the SCM model groups at different time points,the expression level of miR-223 in the myocardial tissue gradually increased with the extension of stimulation time.Compared to the Normal group,mice in the SCM group,miR-223 antagomir NC group,and miR-223 antagomir group exhibited varying degrees of myocardial damage.The expression levels of cardiac injury markers cTnⅠ,BNP,CK-MB,and inflammatory factors IL-6,IL-1 β,and TNF-α in serum were elevated,and the differences were statistically significant(P<0.05).When compared to the SCM group,there were no significant differences in various indicators between the miR-223 antagomir NC group(P>0.05).In the miR-223 antagomir group,the degree of pathological damage in the myocardial tissue was reduced,and the levels of cardiac injury markers cTnⅠ,BNP,CK-MB,and inflammatory factors IL-6,IL-1β,and TNF-α decreased,with statistically significant differences(P<0.05).The results of correlation analysis showed that the expression of miR-223 in mice was positively correlated with the expression of cardiac injury markers cTnI,BNP,CK-MB,and inflammatory factors IL-6,IL-1β,and TNF-α.Conclusion:Downregulation of miR-223 expression can provide protection to the myocardium of SCM mice by alleviating the inflammatory response.