DL-3-n-Butylphthalide reduces atrial fibrillation susceptibility by inhibiting atrial structural remodeling in rats with heart failure.
Hui-Liang QiuHuanlin WuJin MaHaiming CaoLihua HuangWencong QiuYing PengChunhua DingPublished in: Naunyn-Schmiedeberg's archives of pharmacology (2017)
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.
Keyphrases
- atrial fibrillation
- heart failure
- catheter ablation
- left atrial
- oral anticoagulants
- signaling pathway
- oxidative stress
- left atrial appendage
- direct oral anticoagulants
- acute heart failure
- left ventricular
- body weight
- coronary artery
- percutaneous coronary intervention
- poor prognosis
- pi k akt
- rheumatoid arthritis
- minimally invasive
- computed tomography
- clinical trial
- risk assessment
- coronary artery disease
- coronary artery bypass
- transforming growth factor
- pulmonary hypertension
- pulmonary artery
- randomized controlled trial
- combination therapy
- newly diagnosed
- long non coding rna
- gestational age
- epithelial mesenchymal transition
- anti inflammatory
- acute coronary syndrome
- double blind
- surgical site infection