Hyperglycemia-induced myocardialfibrosis may be associated withpyroptosis and apoptosis of cardiomyoctes in diabetic mice br

Myocardialfibrosis is an important manifestation of diabetic cardiomyopathy. This study investigated thepotential mechanism of diabetic myocardialfibrosis. Male C57BL/6J and db/db mice aged 8 weeks were randomlydivided into the diabetic (DB) and control groups. At 20 weeks, the mouse heart was harvested and subjected tohematoxylin-eosin staining (HE) and Masson staining to investigate the degree offibrosis. The expressions oftransforming growth factor-beta 1 (TGF-beta 1), collagen-III, B-cell lymphoma-2 (Bcl2), Bcl2-associated X protein (Bax),cleaved gasdermin D (GSDMD), cysteinyl aspartate specific proteinase-1 (caspase-1), apoptosis-associated speck-likeprotein containing a CARD (ASC), and nucleotide-binding oligomerization domain (NOD)-like receptor 3 (NLRP3)were measured by western blotting. Immunohistochemistry and TdT-mediated dUTP nick end labeling (TUNEL)staining were performed to analyze the development of apoptosis and pyroptosis. A significant increase in bodyweight and blood glucose in the DB group was observed. Myocardial pathological injury,fibrosis, apoptosis, andpyroptosis were more obvious and serious in the DB group. The expression of anti-apoptotic Bcl2 significantlydecreased, while the expression levels of pro-apoptotic Bax, caspase-3, and pyroptosis-related proteins, such as cleavedGSDMD, and caspase-1 in the DB group were significantly increased. Pyroptosis and apoptosis were probably themain mechanisms that caused myocardialfibrosis in mice with diabetes