贾单单,田振军.间歇运动激活LIF/LIFR/STAT3信号促进心梗大鼠心脏血管新生[J].北京体育大学学报,2018,41(7):56-63.
间歇运动激活LIF/LIFR/STAT3信号促进心梗大鼠心脏血管新生
Interval Exercise Activates LIF/LIFR/STAT3 Signaling to Promote Myocardial Angiogenesis in Myocardial Infarction Rats
投稿时间:2018-01-04  
DOI:10.19582/j.cnki.11-3785/g8.2018.07.008
中文关键词:  关键词:心肌梗死  间歇运动  白血病抑制因子  血管新生  大鼠
英文关键词:Keywords: myocardial infarction  interval exercise  Leukemia inhibitory factor  myocardial angiogenesis  rat
基金项目:国家自然科学基金资助项目(编号:31671240, 31371199)。通信作者:田振军。
作者单位
贾单单 陕西师范大学体育学院暨运动生物学研究所陕西 西安 710119 
田振军 陕西师范大学体育学院暨运动生物学研究所陕西 西安 710119 
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中文摘要:
      摘要:目的:探讨间歇运动对心肌梗死(myocardial infarction,MI)大鼠白血病抑制因子(Leukemia inhibitory factor,LIF)表征和心脏血管新生的影响及其可能机制。方法:3月龄SD雄性大鼠,随机分为正常对照组(Control)、间歇运动组(CE)、假心梗组(Sham)、心梗安静组(MI)和心梗+间歇运动组(ME),每组12只。Control组和CE不手术。各心梗组采用左冠状动脉前降支结扎法制备MI模型。运动组在术后1周进行预适应运动(10~15 m/min,30 min/d×5 d/周)。间歇运动采用低强度和高强度依次交替的跑台训练,以10 m/min×10 min进行热身运动,以25 m/min×7 min和15 m/min×3 min依次进行中等强度与大强度交替的间歇运动(60 min/d×5 d/周×8周)。训练结束后次日,血流动力学检测心功能,迅速摘取心脏,RT-qPCR检测心肌LIF/LIFR mRNA表达,Western blot检测心肌LIF、LIFR、p-STAT3/STAT3、VEGF蛋白表达,免疫荧光和免疫组化检测vWF和CD31表达,酶活性试剂盒检测心肌细胞代谢指标。结果:1)间歇运动可激活正常大鼠心肌LIF/LIFR/STAT3通路;2)心梗大鼠心肌LIF/LIFR基因与蛋白表达和STAT3磷酸化水平升高,血管发生代偿性新生,心肌CVF%显著增加,心肌细胞代谢紊乱;3)间歇运动进一步显著上调心梗心肌LIF/LIFR基因与蛋白表达和STAT3磷酸化水平,促进血管新生,显著降低CVF%,改善心肌代谢紊乱。结论:间歇运动显著升高正常和心梗大鼠心肌LIF/LIFR基因和蛋白的表达,其下游信号通路蛋白STAT3的磷酸化水平显著升高,显著刺激心脏的血管再生,改善心梗大鼠心功能。
英文摘要:
      Abstract: Objectives: The aim of this study was to investigate the effects of interval exercise on the expression of Leukemia inhibitory factor (LIF) and angiogenesis in the heart of rats with myocardial infarction (MI). Methods: Three-month male Sprague-Dawley rats were randomly divided into five groups (n = 12): sedentary control group (Control), interval exercise group (CE), sham-operated group (Sham), sedentary MI group (MI) and MI with interval exercise group (ME). The MI model was established by ligation of the left anterior descending coronary artery. One week after MI, the rats in CE and ME were subjected 8 weeks interval training. In the second day after the end of training, the cardiac function were measured by haemodynamics; the mRNA expression of LIF/LIFR was measured by RT-qPCR; the proteins expressions of LIF, LIFR, p-STAT3/STAT3 and VEGF-A were determined by Western Blot; the protein expressions of vWF and CD31 were detected by immunofluorescence or immunohistochemical measurement; and the myocardial metabolism was measured by ELISA kit. Results: 1) Interval exercise can activate the myocardial LIF/LIFR/STAT3 pathway in normal rats; 2) the expression of LIF/LIFR gene and protein and the level of phosphorylation of STAT3 in myocardial infarction rats increased, the blood vessels were compensatory, the CVF% of myocardium increased significantly, and the metabolic disorder of cardiac myocytes was disordered; 3) interval exercise significantly up-regulated the expression of LIF/LIFR gene and protein and the level of STAT3 phosphorylation in myocardial infarction myocardium, promoted angiogenesis, reduced CVF% significantly, and improved myocardial metabolic disorder. Conclusion: Interval exercise significantly increased the expression of LIF/LIFR gene and protein in the myocardium of normal and myocardial infarction rats, and induced the increase of phosphorylation level of downstream signaling pathway protein STAT3, stimulated cardiac regeneration and improved cardiac function in rats with myocardial infarction.
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