早期美托洛尔治疗对急性心肌梗死大鼠心肌炎症因子表达和心功能的影响

目的探讨早期β受体阻断剂—美托洛尔治疗对大鼠急性心肌梗死(AMI)后心肌炎症因子和心功能的影响。方法结扎大鼠左前降支,建立AMI模型,存活随机分为梗死对照组(MI组)和美托洛尔治疗组(MI-B组),另设假手术组(S组)。MI-B组参照中国心脏病研究(CCS-2)方案给予4周美托洛尔治疗,MI组和S组仅以等体积生理盐水灌胃,观察4周后美托洛尔对心肌炎症和心功能的影响。结果与S组相比,MI组心肌组织中促炎性细胞因子TNF-α、IL-1β、IL-10和抗炎性细胞因子IL-10表达明显升与MI组比较,MI-B组心肌细胞内TNF-α和IL-1β表达明显下降,IL-10表达升高,而IL击和浸润心肌组织的淋巴细胞数差异无统计学意义。心脏超声显示MI-B组左室功能明显改善。结论早期美托洛尔治疗AMI可以改善心肌炎症因子表达和心脏功能。美托洛尔有效改善心功能的作用机制至少部分与其降低心肌细胞促炎细胞因子和升高抗炎因子的免疫药理学作用有关。

Effects of early treatment with metoprolol on myocardial inflammatory cytokine expression and heart function in rats with acute myocardial infarction

OBJECTIVE: The aim of study was to explore the effects of early beta-adrenergic blockade-metoprolol treatment on myocardial inflammatory cytokine expression and heart function in rats after acute myocardial infarction (AMI). METHODS: The therapeutic effects of metoprolol on myocardial inflammation and heart function up to 4 weeks (according to the protocol of CCS-2) were studied by the rat model of AMI. Myocardial inflammation was examined by taking account of the number of lymphocytes infiltrated in the myocardium and analyzing the myocardial cytokine production including the pro-inflammatory cytokines: interleukin (IL)-1beta, 6 and tumor necrosis factor (TNF)-alpha and the anti-inflammatory cytokine: IL-10. Echocardiography was used to evaluate heart function. RESULTS: The levels of TNF-alpha, IL-1beta, IL-6 and IL-10 in AMI group were markedly elevated compared to sham rats (P < 0.01) and the cytokines principally excreted by cardiac myocytes. After 4 weeks therapy, metoprolol reduced the production of TNF-alpha and IL-1beta and increased IL-10 levels (P < 0.05) in cardiac myocytes, but had no effect on the number of lymphocytes infiltrated in myocardium. Echocardiography showed that metoprolol markedly improved left heart function (P < 0.05). CONCLUSION: Early metoprolol treatment can improve heart function and myocardial inflammatory cytokine expression after AMI. One immunopharmacologic mechanism underlying the beneficial effects of beta-adrenergic blockade may involve the attenuation of pro-inflammatory cytokines and the increase of anti-inflammatory cytokine levels in cardiac myocytes.