benzofurans and Atrial-Remodeling

Agents against atrial structural remodeling (ASR) are thought to block the occurrence of atrial fibrillation (AF). The aim of this study was to investigate the effects of DL-3-n-butylphthalide (NBP) on ASR and AF formation in rats with heart failure (HF) induced by myocardial infarction. The heart failure rats established 1 week after ligating left anterior descending coronary artery were randomly treated with vehicle (HF group, n = 24), or treated with DL-3-n-butylphthalide (100 mg/kg body weight) (NBP group, n = 26) for 4 weeks. Eighteen rats that underwent the same surgery but without ligating artery treated with vehicle were used as sham group (n = 18). Echocardiography, AF inducibility test, atrial fibrosis, gap junction, cytokine expression and serum antioxidant capacity analysis were detected at follow-up. Treatment of NBP for 4 weeks significantly improved cardiac function (P < 0.05), reduced AF inducibility and duration time (P < 0.05), and attenuated atrial fibrosis (P < 0.05). NBP also up-regulated protein expression of both overall Cx43 and phosphorylated Cx43 (P < 0.05) and improved the distribution of Cx43. Furthermore, NBP significantly inhibited the expression of TNF-α, NF-κB, and TGF-β1 and up-regulated Nrf2 and HO-1 protein expression with an increased serum T-AOC, CAT, and SOD activities and a reduced serum MDA. Collectively, NBP prevented ASR and AF in rats with HF by inhibiting atrial fibrosis, resynchronizing gap junction remodeling through inhibiting TNF-α/NF-κB/TGF-β1-related inflammatory reactions, and up-regulating Nrf2/HO-1-mediated antioxidant effects. Therefore, NBP may be a promising agent as upstream therapy for the prevention of AF.

Topics: Animals; Atrial Remodeling; Benzofurans; Cardiotonic Agents; Heart Atria; Heart Diseases; Heme Oxygenase (Decyclizing); Male; NF-E2-Related Factor 2; NF-kappa B; Rats, Sprague-Dawley; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha