PLGA‐PNIPAM Microspheres Loaded with the Gastrointestinal Nutrient NaB Ameliorate Cardiac Dysfunction by Activating Sirt3 in Acute Myocardial Infarction

Acute myocardial infarction (AMI) is the death of cardiomyocytes caused by a lack of energy due to ischemia. Nutrients supplied by the blood are the main source of cellular energy for cardiomyocytes. Sodium butyrate (NaB), a gastrointestinal nutrient, is a short-chain fatty acid (butyric acid) that may act as an energy source in AMI therapy. Poly(lactic-co-glycolic acid)-Poly (N-isopropylacrylamide) microspheres loaded with NaB (PP-N) are synthesized to prolong the release of NaB and are injected into ischemic zones in a Sprague–Dawley rat AMI model. Here, this study shows that PP-N can significantly ameliorate cardiac dysfunction in AMI, and NaB can specially bind to Sirt3 structure, activating its deacetylation ability and inhibiting the generation of reactive oxygen species, autophagy, and angiogenesis promotion. The results indicate that NaB, acting as a nutrient, can protect cardiomyocytes in AMI. These results suggest that the gastrointestinal nutrient NaB may be a new therapy for AMI treatment, and PP-N may be the ideal therapeutic regimen.