美托洛尔对急性心肌梗死大鼠心肌神经生长因子表达和神经重构的影响

Effects of treatment with metoprolol on myocardial nerve growth factor expression and sympathetic sprouting in rats with acute myocardial infarction

目的探讨β受体阻滞剂美托洛尔对大鼠急性心肌梗死（AMI）后心肌神经生长因子（NGF）表达和交感神经再生的影响。方法结扎大鼠左前降支，建立AMI模型，存活者随机分为美托洛尔治疗组（MI-B组，n=10）和梗死对照组（MI—C组，n=10），另设假手术组（S组，n=8）。MI—B组给予4周美托洛尔治疗，MI-C组和S组给予同体积生理盐水静脉注射和灌胃，4周后检测梗死周边区和梗死远端心脏神经纤维分布和密度以及心肌NGF基因和蛋白表达的变化。结果与S组相比，MI—C组梗死周边和梗死远端心肌组织中NGF基因和蛋白表达明显升高（P〈0．05），梗死周边和梗死远端神经支配密度增高（P〈0．01）。与MI—C组比较，MI—B组心肌细胞内NGF表达明显下降（P〈0．05），神经支配密度亦明显下降（P〈0.01）。结论早期美托洛尔治疗AMI可以改善心肌NGF表达和交感神经再生。美托洛尔改善交感神经再生的作用机制至少部分与其降低神经生长因子的表达和释放作用有关。

Objective The aim of this study was to explore the effects of β receptor antagonist metoprolol on myocardial nerve growth factor expression and sympathetic nerve sprouting in rats after acute myocardial infarction（AMI）. Methods Myocardial infarction was induced by ligation of the left anterior descending coronary artery in 20 rats,which were randomized to MI control group （MI-C ,n = 10） and metoprolol treatment group （MI-B,n = 10）. Sham-operated group （S,n=8） was taken randomly as non-infarction control. After four-week treatment with the drug and placebo, the hearts were removed and examined for nerve fiber density . The nerve growth factor expression was measured using Western blot analysis and reverse transcription polymerase chain reaction （RT-PCR）. Results The density of nerve fibers with positive immunostaining for growth associated protein 43 （GAP43） and tyrosine hydroxylase （TH） increased in MI-C group compared with the S group after AMI both in the peri-infaret and remote area （ P 〈 0. 01 ）. Treatment of AMI rats with metoprolol clearly resulted in reduction in Gap43 and TH（P 〈 0. 01 ）. The level of NGF in MI-C group was also markedly elevated compared with sham rats（ P 〈 0. 05 ）. After 4-week therapy, metoprolol reduced the production of NGF in the peri-infaret and remote area（ P 〈 0. 05 ）. Conclusion Early metoprolol treatment after AMI can improve sympathetic sprouting,which is related to inhibition of NGF expression.