Protective Effect of Metformin on Sepsis Myocarditis in Zebrafish.

ABSTRACT

PURPOSE: We found in previous study that metformin could treat sepsis myocarditis in a mouse model. We employed the zebrafish model organism to investigate the effect of metformin on sepsis myocarditis. METHODS AND RESULTS: Wild-type zebrafish was used to establish a sepsis myocarditis model and combined with image software analysis and cytokine detection, the protective dose of metformin was determined. The results showed that immersion with Escherichia coli could cause 75% mortality in zebrafish and make larvae appear as characteristics of severe sepsis myocarditis. Pretreatment with 10 mM metformin for 3 hours could effectively reduce heart congestion and swelling in zebrafish with sepsis myocarditis and increased the heart rate. It could reduce the mortality and prolong the survival time of zebrafish with sepsis myocarditis; Tg(mpx EGFP) transgenic zebrafish were adopted to explore the number of neutrophils in zebrafish heart before and after metformin protection, and metformin could maintain the number of neutrophils in zebrafish heart; quantitative real-time reverse transcription-polymerase chain reaction showed that metformin could reduce the expression of pro-inflammatory factors, tumor necrosis factor-α and interleukin (IL)-6, and could promote the anti-inflammatory factor, transforming growth factor-ß and IL-10 expression. CONCLUSION: We established a zebrafish sepsis myocarditis model and applied metformin in advance to provide a protective effect on the zebrafish heart.