| Popis: |
ObjectiveDiabetic cardiomyopathy (DCM), characterized by cardiomyopathy with the absence of coronary artery disease, hypertension, and valvular heart disease in patients with diabetes, significantly increases the risk of heart failure. Galectin-3 (Gal-3) has been shown to regulate cardiac inflammation and fibrosis, but its role in DCM remains unclear. This study aimed to determine whether Gal-3 inhibition attenuates DCM and NF-κB p65 activation.MethodsDiabetic cardiomyopathy (DCM) was established by intraperitoneal (IP) injection of streptozotocin for 5 consecutive days in mice. Myocardial injury markers, such as creatine kinase isoenzyme (CK-BM) and lactate dehydrogenase, were detected using ELISA. We used non-invasive transthoracic echocardiography to examine cardiac structure and function. Histological staining was used to explore myocardial morphology and fibrosis. Profibrotic markers and inflammatory cytokines were detected by ELISA and real-time PCR in vivo. The terminal deoxyribonucleotide transferasemediated dUTP nick end-labeling (TUNEL) and immunofluorescence assays were conducted to examine myocardial apoptosis and oxidative stress. Inflammatory cytokines induced by high glucose (HG) were also found in RAW264.7 macrophages. The underlying molecular mechanisms were determined using immunofluorescence and Western blotting analyses.ResultsThe Gal-3 knockdown was observed to ameliorate myocardial apoptosis, oxidative stress, inflammatory cytokines release, macrophage infiltration, and fibrosis, thus, decreasing cardiac dysfunction in DCM mice. In addition, the silence of Gal-3 could suppress macrophage infiltration and inflammatory cytokine release induced by HG. Finally, a Gal-3/NF-κB p65 regulatory network was clarified in the pathogenesis of DCM.ConclusionThe Gal-3 may promote myocardial apoptosis, oxidative stress, inflammation, and fibrosis in vivo and in vitro by the mechanism of reduction of NF-κB p65 activation. |
