Objective:This study aimed to assess the role of miR-129-5p expression in sepsis-induced cardiac inflammation and dysfunction.Methods:Twenty-four 8-week-old C57/BL6 male mice were randomly divided into 4 groups,including normal group,lipopolysaccharide(LPS)group,LPS+mini NC group,and LPS+miR-129-5p mini group(n=6 in each group).A sepsis mouse model was constructed by intraperitoneal injection of LPS.Myocardial injury was assessed by HE staining,immunohistochemistry for PAX6,as well as automatic biochemical analysis for serum levels of creatine kinase(CK)and CK-MB.Primary cardiomyocytes exposed to LPS were established to simulate sepsis-induced cardiac dysfunction in vitro,and were divided into control group,LPS+inhibitor-NC+si-NC group,LPS+inhibitor-NC+si-PAX6 group,LPS+si-NC+miR-129-5p inhibitor group,and LPS+miR-129-5p inhibitor+si-PAX6 group.The degree of apoptosis was analyzed by TUNEL,and the expression of Bcl-2,PAX6 and ZEB2 protein was assessed by Western blotting.Levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β were determined by real-time fluorescence quantitative PCR(RT-qPCR).Results:Compared with normal group,serum levels of CK and CK-MB,cross-sectional area of myocardial cells,percentage of TUNEL or PAX6 positive cells,and PAX6 mRNA expression were significantly higher in LPS group(P＜0.05).Compared with LPS group,these measuremnts were lower in LPS+miR-129-5p minic group(P＜0.05).Furthermore,compared with control group,the percentage of TUNEL positive cells,and expression of PAX6 and ZEB2 proteins and TNF-α,IL-6 and IL-1β mRNA were increased(P＜0.05),whereas and the expression of Bcl-2 protein was decreased significantly in LPS+inhibitor-NC+si-NC group(P＜0.05).Compared with LPS+si-NC+miR-129-5p inhibitor group,the percentage of TUNEL positve cells,and the expression levels of PAX6 and ZEB2 protein and TNF-α,IL-6 and IL-1β mRNA were reduced(P＜0.05),and the expression of Bcl-2 protein was elevated significantly in LPS+miR-129-5p inhibitor+si-PAX6 group(all P＜0.05).Conclusion:MiR-129-5p may regulate myocardial inflammatory reaction through the PAX6/ZEB2 signal pathway,participating in the pathological process of cardiac dysfunction in sepsis mice.
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