丁基苯酞对心力衰竭大鼠心房颤动的影响及作用机制

为探讨丁基苯酞(DL-3-N-butylphthalide,NBP)对心肌梗死诱导的心力衰竭(heart failure,HF)大鼠心房结构重塑和心房颤动形成的影响,本研究将心力衰竭模型大鼠随机分为丁基苯酞组(NBP)、模型组(Model)和假手术组(Sham)。将丁基苯酞用大豆油溶解,制成10 mg/mL的丁基苯酞溶液。丁基苯酞组按照80 mg/kg体重对SD大鼠进行灌胃,模型组和假手术组用等量的大豆油灌胃。假手术组大鼠接受相同手术但未结扎左前降支冠状动脉。分别检测大鼠的超声心动图、心房颤动诱导性试验及心房纤维化,并检测TNF-α、TGF-β1、NF-κB、Nrf2和HO-1的蛋白表达。研究显示,应用丁基苯酞治疗4周后,NBP组大鼠心功能显著改善(p<0.05);NBP组大鼠心房颤动诱导能力和持续时间显著降低(p<0.05);NBP组大鼠心房纤维化程度显著减轻(p<0.05)。丁基苯酞显著抑制TNF-α,NF-κB和TGF-β1的蛋白表达,并上调Nrf2和HO-1的蛋白表达。并且,NBP对TNF-α/NF-κB/TGF-β1和纤维化的抑制作用可能与Nrf2/HO-1信号通路的激活有关。因此,丁基苯酞有望成为预防房颤的上游治疗中的有效药物。

Effect of DL-3-N-butylphthalide on Atrial Fibrillation in Rats with Heart Failure and Its Mechanism

To investigate the effects of DL-3-N-butylphthalide(NBP)on atrial structural remodeling and atrial fibrillation in rats with heart failure(HF)induced by myocardial infarction.Rats with heart failure were randomly divided into DL-3-N-butylphthalide group(NBP),model group(Model)and sham operation group(Sham).The NBP was dissolved in soybean oil to prepare a 10 mg/mL NBP solution.The rats in the NBP group were orally administered with 80 mg/kg body weight,and the model group and the sham operation group were intragastrically administered with the same amount of soybean oil.The sham-operated rats underwent the same procedure but did not ligature the left anterior descending coronary artery.The echocardiogram,atrial fibrillation induction test and atrial fibrosis in rats were observed,and the protein expressions of TNF-α,TGF-β1,NF-κB,Nrf2 and HO-1 were detected.The study showed that after 4 weeks of treatment with NBP,the cardiac function of NBP group was significantly improved(p<0.05);The inducing ability and duration of atrial fibrillation in NBP group were significantly decreased(p<0.05);The degree of atrial fibrosis in NBP group rats was significantly reduced(p<0.05).NBP significantly inhibited the protein expression of TNF-α,NF-κB and TGF-β1,and up-regulated the protein expression of Nrf2 and HO-1.Moreover,the inhibitory effect of NBP on TNF-α/NF-κB/TGF-β1 and fibrosis may be related to the activation of Nrf2/HO-1 signaling pathway.Therefore,NBP is expected to be an effective drug in the prevention of atrial fibrillation.