Irisin ameliorates myocardial ischemia-reperfusion injury through modulation of gut microbiota and intestinal permeability in rats

Abstract

Abstract Purpose Irisin has a significant protection the myocardial from ischemia reperfusion (I/R) injury. Recent studies have suggested that the gut microbiota plays an important role in the progression of myocardial I/R injury. In this context, the aim of this study is to investigate whether Irisin interferes in gut microbiota and gut mucosal barrier during myocardial I/R injury. Methods All the rats received intraperitoneal injection of irisin or PBS, and then myocardial I/R rats disease model was established. Gut microbiota was analyzed by 16S rRNA high-throughput sequencing to assess changes in the microbiota. Colon and ileum tissue structural damage and apoptosis were evaluated by HE staining and Tunnel, respectively. Intestinal barrier integrity was valuated using by immunofluorescence to detecte the protein expression of ZO-1 and occludin and serum lipopolysaccharide. The proinflammatory cytokines (IL-1β, IL-6, TNF-α) in the colon and ileum tissue by Western Blot. Myocardial HE staining and serum cTnI, CK were performed to evaluate the cardiac function. Results Irisin treatment significantly improved the imbalance of intestinal flora in I/R rats. And irisin maintained intestinal barrier function by increasing the expression of ZO-1 and occludin protein in colon and ileum and and decreasing serum LPS concentration. Meanwhile, intestinal inflammation in I/R rats was attenuated by irisin. More importantly, irisin was protective against I/R injury in vivo. Conclusion Irisin intervention could improve the impaired gut mucosal barrier and reduce the production of LPS after I/R through regulating gut microbiota, thus inhibiting the inflammation and finally exerted the cardioprotective effect.