脑源性神经营养因子对运动诱导的心梗后大鼠心肌血管生成的介导作用
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江苏省科技厅科研基金(BE2011793)


Involvement of brain⁃derived neurotrophic factor(BDNF)in exercise⁃induced angiogenesis in post⁃myocardial infarction rat hearts
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    摘要:

    目的:研究脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)对运动诱发的心梗后心肌血管生成的介导作用。方法:12周龄雄性SD大鼠48只,选取12只为假手术对照组(Sham),只开胸穿线不结扎;余下大鼠永久性结扎左冠状动脉前降支后,随机分为心梗安静组(MIC)、心梗+运动组(MIE)、心梗+运动+BDNF特异性高亲和力受体原肌球蛋白激酶受体B(tyrosine kinase receptor B,TrkB)阻滞剂K252a腹腔注射组(MIEK),每组12只。术后1周尾静脉采血、心彩超检查后进行为期8周的有氧运动训练,训练结束行心彩超检查后腹腔麻醉取材,ELISA检测血清BDNF水平,免疫组化检测心肌梗死周围区BDNF表达及心肌血管密度,PCR和Western blot分别检测心肌BDNF mRNA和蛋白水平,Western blot检测心肌TrkB蛋白表达及磷酸化水平。结果:运动促进梗死周围区BDNF mRNA(P < 0.01)和蛋白(P < 0.01)表达,同时诱导TrkB磷酸化(P < 0.01),用K252a阻断BDNF受体可抑制TrkB激活(P < 0.01),同时逆转运动诱发的心肌血管生成(P < 0.01)和心功能改善(P < 0.05);大鼠血清BDNF水平与心肌血管密度(r=0.501,P=0.007)、心脏EF值(r=0.611,P=0.002)呈正相关,血清BDNF运动前后变化幅度与其EF值变化呈正相关(r=0.498,P=0.015)。结论:BDNF在心梗后运动诱发的心肌血管生成效应中发挥重要介导作用。

    Abstract:

    Objective:To investigate the contribution of BDNF to exercise-induced angiogenesis in post-myocardial infarction rat hearts. Methods:Forty eight male SD rats(12 weeks old)were randomly divided into the following experimental groups:a sham infarction(Sham)group,a sedentary MI(MIC)group,a MI+exercise(MIE)group,a MI+exercise+K252a(MIEK)group. The MI model was established by ligation of the left anterior descending coronary artery,and exercised rats received 8 weeks of treadmill running. At the end of the exercise protocol,BDNF mRNA and protein expression(Western blot,RT-PCR and immunostaining)were measured,tropomyosin-related kinase B(TrkB)protein expression and phosphorylation levels were measured by Western blot,the angiogenic response was investigated by immunostaining,and cardiac function was analyzed by echocardiography. Results:Exercise training upregulated BDNF mRMA(P < 0.01)and protein(P < 0.01)expression,as well as phosphorylated TrkB levels(P < 0.01)in post-MI rat hearts. Exercise training induced elevation of serum BDNF in post-MI rats,which were related to angiogenesis(r=0.501,P=0.007)and cardiac function(r=0.611,P=0.002). The exercise-related angiogenic response(P < 0.01)and functional improvement(P < 0.05)was attenuated by inhibition of BDNF receptor. Conclusion:Exercise convey its pro-angiogenic effects in ischemic myocardial tissue through BDNF.

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王碧蕾,金 虹,韩熙琼,夏 扬,刘乃丰.脑源性神经营养因子对运动诱导的心梗后大鼠心肌血管生成的介导作用[J].南京医科大学学报(自然科学版),2018,(6):758-764

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  • 收稿日期:2018-04-13
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  • 在线发布日期: 2018-06-22
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