β受体阻滞剂对兔心肌梗死后酪氨酸羟化酶mRNA表达及心脏电生理的影响

Effects of beta-blocker on Expression of Tyrosine Hydroxylase mRNA and Electrophysiological Study in a Rabbit Myocardial Infarction Model

目的通过美托洛尔对兔心肌梗死后心肌酪氨酸羟化酶(tyrosine hydroxylase,TH) mRNA表达水平的影响来探讨β受体阻滞剂改变心脏电生理的可能机制。方法30只新西兰兔结扎冠状动脉制作兔心肌梗死模型后随机分成2组,每组15只,美托洛尔组(Metoprolol组)给予倍他乐克(10 mg·kg^(-1)·d^(-1)),而对照组(MI组)给予NS(5 ml·kg^(-1)·d^(-1))灌胃。再选取12只兔开胸冠状动脉穿线不结扎作为假手术组(Sham组)。8周后所有成活的兔均进行电生理试验,并采用RT- PCR检测心肌的TH mRNA表达水平。结果Sham组室性心律失常诱发率为16．7%,而MI组室性心律失常的诱发率上升至58．3%,经过美托洛尔治疗后其诱发率又降至8．3%。MI组梗死灶周及非梗死左室游离壁TH mRNA水平分别为(0．848±0．064,0．863±0．062),明显高于Sham组对应部位(0．672±0．051,0．653±0．054);经过8周美托洛尔治疗后TH mRNA相对表达水平分别降至(0．715±0．032,0．692±0．049)。结论美托洛尔治疗可降低心肌梗死后TH mRNA表达水平,可能改善了交感神经重构,减少去甲肾上腺素的合成,改善心脏电生理异质性,降低室性心律失常发生率。

Objective To evaluate the effects of prolonged metoprolol treatment on the expression levels of tyrosine hydroxylase （TH） mRNA and electrophysiological characterization in post myocardial infarction. Methods MI was induced by ligation of the coronary artery in 30 Rabbits, and sham operations were performed in 12 control animals. Metoprolol was then administered to 15 of the MI animals. After standard electrophysiological recordings, RT-PCR was applied to observe the expression levels of TH mRNA. Results Eight weeks after MI, 16.7 % （2/12）rabbits were induced to ventricular arrhythmias; metoprolol treatment obvionsly reduced the increased incidence of post-MI ventricular arrhythmias compared to those without treatment （8.3% vs. 58.3%, P 〈0.001 ）. The expression levels of TH mRNA increased in MI group compared with Sham group, and were reduced by metoprolol treatment. Conclusion Long-term metoprolol treatment appears to reduce the expression level of TH mRNA in post myocardial infarction, and these may improve electrophysiological heterogeneity which partly decreased the incidence of ventricular arrhythmias.