游泳运动通过Sirt1信号减轻小鼠心肌梗死后心脏病理性重塑

Swimming alleviates cardiac pathological remodeling after myocardial infarction via Sirt1 signaling in mice

目的:探讨游泳运动(Sw)调控沉默信息调节因子1(Sirt1)信号减轻小鼠心肌梗死(MI)后心脏病理性重塑的作用。方法:采用冠状动脉左前降支结扎制备小鼠MI模型,随机分为4组:假手术组、MI组、MI+Sw组和MI+Sw+EX527(Sirt1抑制剂)组。游泳运动采用无负重游泳9周,检测左室内压最大上升和下降速率(±dp/dt_(max)),HE和Masson染色观察心肌结构和纤维化程度,TUNEL染色检测细胞凋亡率,RT-qPCR检测炎症因子TNF-α、IL-1β和IL-6的mRNA水平,Western blot检测cleaved caspase-3、Bcl-2、Bax、Sirt1、Ac-NF-κB和NF-κB蛋白水平。结果:与假手术组相比,MI组±dp/dt_(max)显著降低(P<0.01),心肌纤维排列紊乱、断裂,纤维化程度、TUNEL阳性细胞数以及TNFα、IL-1β、IL-6的mRNA水平均显著增加(P<0.01),同时,cleaved caspase-3、Bax和Ac-NF-κB的表达增加,Bcl-2和Sirt1表达降低(P<0.01);与MI组相比,MI+Sw组±dp/dt_(max)增加,心肌纤维排列改善、断裂减轻,纤维化、TUNEL阳性细胞数以及TNF-α、IL-1β、IL-6的mRNA水平均降低(P<0.01),Bcl-2和Sirt1表达增加,cleaved caspase-3、Bax和AcNF-κB降低(P<0.01);而与MI+Sw组相比,EX527显著阻断了游泳运动对心肌梗死后小鼠心脏病理性重塑的抑制和对Sirt1、NF-κB信号的调控作用。结论:游泳运动可通过调控Sirt1信号抑制炎症反应、改善小鼠心肌梗死后心脏病理性重塑。

ATM:To investigate the effect of swimming(Sw)on cardiac pathological remodeling after myocardial infarction(MI)via regulating Sirt1 signaling in mice.METHODS:Myocardial infarction was induced by ligation of the left anterior descending coronary artery.The mice were randomly divided into four groups:sham group,MI group,MI+Sw group and MI+Sw+EX527 group.The exercise group was arranged to no-load swimming training weight for 9 weeks.The maximal left ventricular pressure rising rate(+dp/dt_(max))and the maximal left ventricular pressure decreasing rate(−dp/dt_(max))were detected.Myocardial structure and fibrosis were observed by HE and Masson staining.Apoptotic rate was observed by TUNEL staining.The mRNA levels of inflammatory factors including TNF-α,IL-1βand IL-6 were detected by RT-qPCR.Western blot was used to detect the expression levels of Bcl-2,Bax,cleaved caspase-3,Sirt1,AcNF-κB and NF-κB.RESULTS:Compared with sham group,±dp/dt_(max) in MI group were significantly decreased,myocardial fiber arrangement was disorder and rupture,myocardial fibrosis and apoptosis were also increased(P<0.01).In addition,the mRNA levels of TNF-α,IL-1βand IL-6 were increased,the expression of Sirt1 and Bcl-2 were decreased while the expression of Ac-NF-κB,cleaved caspase-3,and Bax were increased(P<0.01).Compared with MI group,±dp/dt_(max) in MI+Sw group were significantly increased,myocardial fiber arrangement,fibrosis and apoptosis were alleviated.The mRNA levels of TNF-α,IL-1βand IL-6 were also decreased,the expression of Sirt1 and Bcl-2 were increased while the expression of Ac-NF-κB,cleaved caspase-3,and Bax were decreased(P<0.01).EX527 could block the effects of swimming on MI-induced cardiac pathological remodeling and Sirt1/NF-κB pathway regulation.CONCLUSION:Swimming could alleviate cardiac pathological remodeling after myocardial infarction by inhibiting inflammatory response via Sirt1 pathway in mice.