Abstract

Background Inflammation, oxidative stress , and apoptosis contribute to myocardial ischemia/reperfusion injury (I/RI). Alpha-lipoic acid (ALA) plays a critical role in I/RI by impeding apoptosis and inflammation. Here, we aimed to explore the underlying mechanisms of ALA after I/RI. Methods The left anterior descending coronary artery (LAD) was ligated, and H9c2 cells were exposed to hypoxia/reoxygenation (H/R) to establish an I/RI model. Prior to this, H9c2 cells and rats were treated using an appropriate amount of ALA. The cardiac function, inflammatory factors, and myocardial pathology were assessed in vitro . We detected cell viability , apoptosis, and oxidative stress-related factors in vivo . Moreover, proteins of the HMGB1/TLR4/NF-κB signaling pathway were detected both in vivo and in vitro . Results We observed that ALA increased cell viability in vitro and decreased apoptosis in vitro and in vivo . ALA inhibited reactive oxygen species production, decreased malondialdehyde , and increased superoxide dismutase activity to resist oxidative stress in vitro . ALA also reduced the expression of inflammatory cytokines (IL-6, IL-1β, and TNF-α) in vivo . ALA also suppressed the levels of the apoptotic protein, Bax, and increased the expression of the anti-apoptotic protein Bcl-2, in vitro and in vivo . Moreover, we observed that ALA significantly inhibited the cytoplasmic localization of HMGB1 , which might attenuate MI/RI or H/R via HMGB1/TLR4/NF-κB pathway. Conclusion ALA regulates HMGB1 translocation and attenuates I/R via the HMGB1/TLR4/NF-κB signaling pathway, thus impeding apoptosis, oxidation, and inflammation, and might be a potential target for myocardial ischemia/reperfusion injury.