美托洛尔对心肌梗死兔自主神经重构的影响
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山东省卫生科技发计划项目(2003HZ118)


Effects of Metoprolol Treatment on Neural Remodeling After Myocardial Infarction in Rabbits
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    目的探讨β受体阻滞剂美托洛尔治疗对心肌梗死后心脏自主神经重构的改善作用。方法通过结扎新西兰大白兔冠状动脉前降支制作心肌梗死模型,随机分成心肌梗死+美托洛尔组[(10mg/(kg·d),治疗组)、心肌梗死组(模型组)和假手术组。8周后所有成活兔均进行统一的电生理检查,诱发室性心律失常。并处死实验动物,取心肌采用免疫组织化学的方法观察心室神经纤维的形态、密度及生长活性。结果模型组室性心律失常诱发率明显高于假手术组(58.3%比16.7%,p<0.001),而美托洛尔治疗后其诱发率降至8.3%。模型组梗死灶周S100及GAP43阳性神经纤维密度分别达到3889±521μm2/mm2和3090±622μm2/mm2,明显高于假手术组(1727±304μm2/mm2和718±177μm2/mm2;P均<0.01),且神经纤维空间分布紊乱;而治疗组梗死灶周S100及GAP43阳性神经纤维密度降至2725±283μm2/mm2和1922±508μm2/mm2,与模型组比差异均有统计学意义(p<0.05),且神经形态及分布更类似于假手术组,非梗死左心室游离壁心肌梗死后密度上调的S100及GAP43阳性神经纤维经美托洛尔治疗后也明显下降(p<0.05)。结论美托洛尔可改善心肌梗死动物模型的神经重构,从而可能预防心肌梗死后室性心律失常的发生。

    Abstract:

    Aim To investigate the influence of β-blocker (metoprolol) on the ventricular neural remodeling and susceptibility to ventricular arrhythmias. Methods New Zealand rabbits were ligated with left anterior descending branch for myocardial infarction (MI) induction. The rabbits were randomized to metoprolol group treated with metoprolol [10 mg/(kg·d)], MI group and sham operation group. All groups were further followed up for 8 weeks. After electrophysiological recordings, immunostaining was applied to detect the shape and density of nerve fibers. Results Eight weeks after operation, metoprolol treatment reduced the increased incidence of post-MI ventricular arrhythmias compared with those placebo treatment (8.3% vs 58.3%, p<0.001). The densities of S100 and GAP43 positive nerve fibers (3 889±521 μm2/mm2, 3 090±622 μm2/mm2) were significantly higher in MI group than in sham operation group (1 727±304 μm2/mm2,718±177 μm2/mm2)at infarct border. Additionally, the distribution of nerve fibers in the MI group were obviously diverse in contrast to sham group. The densities of S100 and GAP43 positive nerve fibers dropped to 2 725±283 μm2/mm2 and 1 922±508 μm2/mm2 at infarct border after meteprolol treatment. Otherwise, metoprolol attenuated the heterogeneity of cardiac innervation. The densities of S100 and GAP43 positive nerve fibers at non-infarct left ventricular free wall were also lowered by meteprolol treatment in MI model. Conclusion Metoprolol appeared to reduce the post-MI ventricular arrhythmias, partly by improving neural remodeling.

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胡和生,闫素华,王清,程文娟,李晓鲁,薛梅,孙雪林.美托洛尔对心肌梗死兔自主神经重构的影响[J].中国动脉硬化杂志,2007,15(3):185~188.

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  • 收稿日期:2006-10-26
  • 最后修改日期:2007-02-09
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