Conclusions
SGLT-2i dapagliflozin may prevent diabetic rats' atrial remodeling and reduce the inducibility of atrial fibrillation partly by targeting TLR4/IRAK1/TRAF6/NF-κB inflammatory pathway.
Methods
A total of 42 rats were randomly assigned into three groups: control group (CON group); diabetes group (DM group): diabetes mellitus rats were established by 65 mg/kg streptozotocin (STZ) intraperitoneal injection; and diabetes + dapagliflozin group (DM + DAPA group): diabetic rats were given DAPA gavage administration (DAPA 2mg/kg/d for 4 weeks by gavage administration), 14 rats in each group. Epicardial multiple-lead recording and intracardiac electrophysiology studies were performed to investigate the electrical remodeling in the heart and the atrial fibrillation inducibility in each group. Western blot analysis and real-time PCR were used to determine the protein and mRNA expression of toll-like receptor 4 (TLR4), interleukin receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor-kappa B (NF-κB), and type I collagen (collagen I).
Purpose
The mechanism of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) reducing the incidence of atrial fibrillation remains unclear. We hypothesize that sodium-glucose cotransporter-2 inhibitor alleviated atrial remodeling in STZ-induced diabetic rats by targeting TLR4 pathway.
Results
Compared with rats in CON group, rats in DM group showed marked myocardial fibrosis, ectopic pacing excitement, reduced conduction velocity, decreased cardiac function. TLR4/IRAK1/TRAF6/NF-κB, collagen I proteins expressions and incidence of atrial fibrillation (27.3%) were increased in DM group. Parts of these changes were reversed by treatment of DAPA. Incidence of atrial fibrillation was decreased in DM + DAPA group (2.8%). Conclusions: SGLT-2i dapagliflozin may prevent diabetic rats' atrial remodeling and reduce the inducibility of atrial fibrillation partly by targeting TLR4/IRAK1/TRAF6/NF-κB inflammatory pathway.