Protective role of matrine in sepsis-associated cardiac dysfunction through regulating the lncRNA PTENP1/miR-106b-5p axis

Abstract

Background: Matrine has attractive cardioprotective effects in some diseases. This study aimed to evaluate the therapeutic potential of matrine against cardiac dysfunction induced by sepsis in vivo and in vitro, and further explore the related mechanisms. Methods: Cecal ligation and puncture (CLP) was used to induce a sepsis mice model, and H9C2 cells treated with lipopolysaccharide (LPS) were used as a cardiac myoblast injury model. The evaluation of cardiac function of mice was performed by measuring cardiac function biomarker levels and hemodynamic indicators. An ELISA method was used to examine inflammatory cytokine levels. H9C2 cell viability was measured using MTT assay. The expression of non-coding RNAs that might be involved in matrine function was analyzed using real-time quantitative PCR. Results: Matrine could significantly improve the cardiac function and attenuate the inflammatory response of the mice model, and could increase H9C2 viability and inhibit inflammation in the cell model. By matrine administration, the expression of PTENP1 was downregulated, but miR-106b-5p expression was upregulated both in vivo and in vitro. The cardioprotective effects of matrine in mice and cell models could be reversed by the overexpression of PTENP1 or the knockdown of miR-106b-5p, and the overexpression of miR-106b-5p could significantly abolish the effects of PTENP1 on cardiac function and inflammation. Conclusion: All the data revealed that matrine can alleviate sepsis-related cardiac dysfunction by enhancing cardiac myoblast viability and attenuating inflammatory responses through the PTENP1/miR-106b-5p axis.

Keywords

• Sepsis
• Cardiac dysfunction
• Matrine
• Inflammation
• LncRNA PTENP1
• miR-106b-5p