EGCG alleviates sepsis-induced myocardial injury by regulating macrophage polarization via the TLR4/MyD88/NF-κB pathway.

OBJECTIVE

To investigate the protective effects of epigallocatechin gallate (EGCG) on sepsis-induced myocardial injury (SIMI) in mice and elucidate its underlying mechanisms.

METHODS

A mouse model of sepsis was established by cecum ligation and puncture (CLP). The cardiac function of mice was detected using echocardiography. Myocardial histopathological changes were observed by hematoxylin-eosin (HE) staining and transmission electron microscopy. The levels of creatine kinase-MB, lactate dehydrogenase, superoxide dismutase, malondialdehyde, and reactive oxygen species were detected in serum and myocardial tissues. The levels of cytokines (IL-10, IL-6, and IL-1β) in serum and myocardial tissue were determined, and immunohistochemistry, CD86/CD206 dual-fluorescence staining combined with western blot analysis were performed to detect the protein expressions of M1 macrophage markers (iNOS, CD86), M2 macrophage markers (Arg-1, CD163, CD206), and related cytokines (TNF-α, IL-10). Furthermore, the protein expression levels of the toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) in myocardial tissue were measured.

RESULTS

EGCG pretreatment significantly improved cardiac function and alleviated myocardial injury. EGCG ameliorated oxidative stress in myocardial tissue. EGCG promoted the polarization of macrophages towards the M2 phenotype and reduced the production of pro-inflammatory cytokines in SIMI mice. EGCG inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway.

CONCLUSION

EGCG exerted protective effects against SIMI in mice by modulating the TLR4/MyD88/NF-κB signaling pathway and promoting M2 macrophage polarization.