DL-3-n-Butylphthalide reduces atrial fibrillation susceptibility by inhibiting atrial structural remodeling in rats with heart failure
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.
KeywordsDL-3-n-Butylphthalide Atrial structural remodeling Heart failure Atrial fibrillation
Sincere thanks to Professor Matt Springer (Cardiovascular Research Institute, University of California, San Francisco; Division of Cardiology, University of California, San Francisco; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco), Dr. Xiaoyin Wang (Cardiovascular Research Institute, University of California, San Francisco) for continued advice, and De-Chun He (Animal Experimental Center, Guangdong Provincial Academy of Chinese Medicine) for careful care of animals and technical assistance.
The conception and design were proposed by Chun-Hua Ding and Ying Peng. Animal experiment was finished by Hui-Liang Qiu, Jin Ma, and Wen-Cong Qiu. Molecular biology experiments were mainly conducted by Hui-Liang Qiu, Wen-Cong Qiu, and Li-Hua Huang. Data collection and analysis were mainly finished by Hui-Liang Qiu and Hai-Ming Cao. Paper was drafted by Hui-Liang Qiu and reviewed by Chun-Hua Ding. Funding was secured by Chun-Hua Ding and Huan-Lin Wu.
The study was supported by joint research project of the Guangdong Provincial Department of Science and Technology and the Guangdong Provincial Academy of Chinese Medicine (No. 2014A020221045), and science and technology research project of the Guangdong Provincial Hospital of Chinese Medicine (No. YN2016MJ04).
Compliance with ethical standards
This study was approved and monitored by the Animal Care Committee of Guangdong Provincial Hospital of Chinese Medicine and was implemented in compliance with the Regulations of Experimental Animal Administrations issued by the State Committee of Science and Technology of the People’s Republic of China.
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