Tanshinone IIA alleviates inflammation and apoptosis in myocardial ischemia-reperfusion injury by modulating the MALT1/NF-κB/NLRP3 signaling axis.

OBJECTIVE: , protects cardiomyocytes against ischemia-reperfusion (I/R) injury. This study aims to elucidate its underlying molecular mechanisms. METHODS: We established a myocardial I/R injury model in rats by coronary artery ligation and created a hypoxia/reoxygenation (H/R) cell model for experimental investigation. The expression levels of relevant genes and proteins were assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. Cellular viability and myocardial tissue damage were evaluated through cell counting kit-8 (CCK-8) assay, biochemical test kits, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, hematoxylin-eosin (HE) staining, and triphenyltetrazolium chloride (TTC) staining. RESULTS: This study demonstrated that Tan IIA treatment significantly reduced serum levels of cardiac troponin T (cTnT), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH) in rats with myocardial I/R injury. It also suppressed the expression of inflammatory factors-tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-18, and IL-6-in myocardial tissue, inhibited apoptosis, diminished myocardial infarct size, and ultimately ameliorated histopathological damage. Meanwhile, in H9C2 cells subjected to H/R injury, Tan IIA treatment enhanced cell viability and attenuated inflammatory response and apoptosis. Mechanistically, Tan IIA downregulated mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), leading to suppressed expression and nuclear translocation of nuclear factor kappa B (NF-κB), which subsequently inhibited the activation of the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3). This cascade alleviated I/R-induced myocardial inflammation and apoptosis, thereby conferring protection against myocardial I/R injury. CONCLUSION: Tan IIA attenuated I/R-induced myocardial inflammation and apoptosis through the inhibition of the MALT1/NF-κB/NLRP3 signaling pathway, ultimately alleviating myocardial I/R injury.