1.Protective Effect of MiR-193a-5p on Cardiac Function in Rats with Chronic Heart Failure by Regulating IL-33/ST2 Signaling Pathway
Peng DING ; Jia LI ; Xiaodan ZHAO ; Jie ZHAO ; Changrong MIAO
Journal of Kunming Medical University 2025;46(5):48-54
Objective To investigate the protective effect of miR-193a-5p on cardiac function and the regulation of IL-33/ST2 signaling pathway in rats with chronic heart failure(CHF).Methods Forty SPF-grade Wistar rats were randomly divided to four groups:Sham group,CHF group,NC group,and miR-193a-5p group,10 rats in each group.The model of chronic heart failure was duplicated in the CHF group,NC group,and miR-193a-5p group.Subsequently,the rats in the NC group and miR-193a-5p group were received 5 nmol/L of NC-agomiR or miR-193a-5p-agomiR,respectively,via tail vein injection every 3 days for 4 weeks.In contrast,the rats in the Sham and CHF groups were received an equal amount of saline injection.At the endpoint of the experiment,doppler color ultrasonography was used to detect the left ventricular posterior wall thicknesses(LVPWs),left ventricular posterior wall thickness at end-diastole(LVPWd),systolic interventricular septal thicknesses IVSs,end-diastolic interventricular septal thicknesses(IVSd),and left ventricular ejection fractions(LVEFs)in the above rats,and the changes in the cardiac phenotypic indices of HW/BW vs.LVW/BW in the 4 groups,and cardiac tissues of the rats of the 4 groups were selected.Histomorphological analysis was performed,and the expression levels of miR-193a-5p in the cardiac tissues of the four groups of the rats were detected by qPCR;apoptosis was detected by Tunel staining;the levels of the inflammatory factors interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-alpha)in the myocardial tissues were measured by Elisa;Western blot was used to detect the expression levels of IL-33 and ST2 protein in myocardial tissues.Results Compared with the Sham group,the hearts in the CHF and NC groups showed increased volume,altered geometry,thinning of the myocardium,and pallor in the infarcted area,whereas the miR-193a-5p group showed partial remission.In addition,the expression levels of miR-193a-5p in cardiac tissues of the CHF and NC groups showed a decreasing trend,whereas showed a significant increase in the miR-193a-5p group(P<0.01).In CHF group and NC group,LVPWs,LVPWd,IVSS,IVSD HW/BW and LVW/BW increased significantly,and LVEF decreased significantly(P<0.01).In miR-193a-5p group,LVPWs,LVPWd,IVSs,IVSd,HW/BW and LVW/BW decreased significantly but higher than sham group,and LVEF increased significantly but lower than sham group(P<0.01).The expression of miR-193a-5p increased significantly in CHF group and NC group,decreased significantly in miR-193a-5p group but still higher than sham group(P<0.01).The expression of IL-33 and ST2 protein increased significantly in CHF group and NC group,and decreased significantly in miR-193a-5p group(P<0.01).Conclusion miR-193a-5p has a protective effect on cardiac function in the rats with chronic heart failure.The mechanism might be related to inhibiting the release of inflammatory factors,reducing cardiomyocyte apoptosis and the inhibition of IL-33/ST2 signaling pathway.

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