摘要
目的:探讨心脏NRG1在间歇运动激活心梗(myocardial infarction,MI)大鼠心肌NRG1-PI3K/Akt通路抑制心肌细胞凋亡的作用。方法:雄性SD大鼠48只,随机分为假手术组(S),心梗安静组(MI),心梗+间歇运动组(ME),心梗+间歇运动+抑制剂组(MEA),每组12只。采用左冠脉前降支结扎法建立MI模型。S组手术仅穿线不结扎。ME组和MEA组在MI术后1周进行跑台间歇运动。运动开始速度为10 m/min运动10 min后,速度逐渐增至25 m/min×7 min,再以15 m/min×3 min运动,之后依次交替进行。60 min×1次/d,5 d/周×8周。训练结束后次日,腹腔麻醉,颈动脉插管测定LVSP、LVEDP及±dp/dtmax。之后开胸摘取心脏,进行组织学制片,Masson染色。荧光实时定量PCR测定心肌NRG1及其受体ErbB2/4表达。Western blot法检测心肌NRG1、ErbB2/4、PI3K/Akt、Bcl-2和Bax蛋白含量。Caspase3表达及TUNEL检测观察分析心肌细胞凋亡情况。结果:MI组胶原容积百分比(CVF)和LVEDP较S组显著升高(P<0.01,P<0.01),LVSP和±dp/dtmax显著降低(P<0.01,P<0.01)。且MI后心肌ErbB4 mRNA表达显著降低(P<0.01),心肌NRG1、ErbB2和ErbB4蛋白表达显著降低(P<0.05,P<0.01,P<0.01),PI3K/Akt蛋白表达及Bcl-2/Bax比值显著降低(P<0.01,P<0.01),TUNEL阳性细胞数和Caspase3活力显著增加(P<0.01,P<0.01)。ME组CVF和LVEDP较MI组显著降低(P<0.01,P<0.01),LVSP和±dp/dtmax显著升高(P<0.01,P<0.01),心肌NRG1、ErbB2和ErbB4 mRNA及蛋白表达均显著增加(P<0.01,P<0.01,P<0.01),PI3K/Akt蛋白表达和Bcl-2/Bax比值显著增加(P<0.01,P<0.01),TUNEL阳性细胞数和Caspase3活力显著降低(P<0.01,P<0.01),且运动效应被抑制剂AG1478显著减弱。结论:间歇运动可通过激活心肌NRG1及其受体表达,上调PI3K/Akt蛋白表达,抑制心肌细胞凋亡和胶原过度增生,改善心功能。
Objectives： This study aimed at discussing the effect of Neuregulin-1（ NRG1） on myocardial NRG1-PI3 K / Akt signaling pathway activated by interval exercise and on myocardial apoptosis inhibited by interval exercise in rats with myocardial infarction. Methods： Forty-eight male Sprague-Dawley rats were randomly assigned to four groups（ n = 12 per group） ： sham-operated group（ S）,myocardial infarction group（ MI）,aerobic interval exercise with myocardial infarction group（ ME）,ME with inhibitor AG1478 group（ MEA）. The MI model was established by ligation of the left anterior descending coronary artery. Rats in ME and MEA groups finished 8-week aerobic interval exercise that initiated 10 min at 10 m / min,and gradually increased to 7 min × 25 m / min,each interval session consisted of 7 min × 25 m / min and 3 min × 15 m / min（ rest）,repeated several times,60 min /day,5 d / week,8 weeks in total. The next day after training,rats were anesthetized,the LVSP,LVEDO and ±dp / dtmax were tested by carotid artery intubation. And the tissue sections of heart were developed with Masson staining. The mRNA expressions of NRG1 and its receptors ErbB 2 /4 were examined by RT-qP CR,the protein expressions of NRG1,ErbB 2 /4,PI3 K / Akt,Bcl-2 and Bax were measured by Western blotting. The level of apoptosis was detected by TUNEL staining and Caspase3 expression. Results： Compared with S group,the CVF and LVEDP of MI group increased（ Ps〈0. 01）,LVSP, ± dp / dtmax,ErbB 4 mRNA expression,protein expressions of NRG1,ErbB 2,ErbB 4,PI3 K / Akt,and Bcl-2 / Bax decreased（ Ps〈0. 05）,and TUNEL positive cells and Caspase3 activity significantly increased（ Ps〈0. 01）. Compared with MI group,the CVF and LVEDP of ME group decreased,LVSP, ± dp / dtma,mRNA and protein expressions of NRG1,ErbB 2 and ErbB 4 increased（ Ps〈0. 01）,PI3 K / Akt protein level and Bcl-2 / Bax also increased（ Ps〈0. 01）,TUNEL positive cells and Caspase3 activity significantly decreased（ Ps〈0. 01）. The e
出处
《北京体育大学学报》
CSSCI
北大核心
2016年第6期69-76,83,共9页
Journal of Beijing Sport University
基金
国家自然科学基金资助项目(编号:31371199
31171141)
陕西师范大学特色发展学科建设项目(师学科2015-1)
