曲马多减少大鼠急性心肌梗死中心肌梗死面积和核因子-κB 的表达和激活。

Tramadol reduces myocardial infarct size and expression and activation of nuclear factor kappa B in acute myocardial infarction in rats.

机构信息

Department of Anesthesiology, Shanxi Medical University, Taiyuan, China.

出版信息

Eur J Anaesthesiol. 2009 Dec;26(12):1048-55. doi: 10.1097/EJA.0b013e32832c785d.

DOI:10.1097/EJA.0b013e32832c785d

PMID:19829116

Abstract

BACKGROUND AND OBJECTIVE

Some anaesthetics show cardioprotective properties, but the underlying mechanism remains elusive. The aim of this study was to investigate the cardioprotective effect of tramadol and the association of the effect with the changes in expression and activation of nuclear factor kappa B (NF-kappaB) in acute myocardial infarction in a rodent model.

METHODS

Male Sprague-Dawley rats were randomly divided into three groups: the sham group, exposure of anterior parts of the heart was carried out without ligation of the coronary artery; coronary artery occlusion (CAO) group, ligation of the left anterior descending branch of the coronary artery was performed; and the group in which the animals were pretreated with tramadol (12.5 mg kg(-1), intravenously) before the CAO (T + CAO). The infarct size, expression of NF-kappaB subunit p65 mRNA and protein and intercellular adhesion molecule-1 mRNA were examined. Isolated nucleus suspension was analysed by flow cytometry to determine activation of NF-kappaB.

RESULTS

The area at risk (percentage of left ventricle) was 46.4 +/- 6.2 and 48.2 +/- 5.9% in the CAO and T + CAO groups, respectively, showing no statistical difference in area at risk/left ventricle between the two groups (P > 0.05). The infarct size (percentage of risk area) was reduced from 44.9 +/- 6.8% in CAO animals to 31.6 +/- 7.7% in T + CAO animals. The reduction of infarct size in the T + CAO group was statistically significant (P < 0.05). Expression of NF-kappaB and its mRNA and intercellular adhesion molecule-1 mRNA was significantly increased in the CAO group compared with the sham group and was significantly decreased in the T + CAO animals. Flow cytometry assay revealed that tramadol attenuated the activation of NF-kappaB by 13.4%.

CONCLUSION

Tramadol may protect myocardium against acute myocardial ischaemic injury and could reduce myocardial infarct size, which may be associated with the expression and activation of NF-kappaB.

摘要

背景与目的

一些麻醉剂具有心脏保护作用，但潜在机制仍不清楚。本研究旨在探讨曲马多对急性心肌梗死模型中啮齿动物的心脏保护作用及其与核因子 kappa B（NF-kappaB）表达和激活变化的关系。

方法

雄性 Sprague-Dawley 大鼠随机分为三组：假手术组，仅暴露心脏前区而不结扎冠状动脉；冠状动脉闭塞（CAO）组，结扎左前降支冠状动脉；以及曲马多预处理组（12.5mg/kg，静脉注射）后行 CAO（T+CAO）。检测梗死面积、NF-kappaB 亚单位 p65mRNA 和蛋白以及细胞间黏附分子-1mRNA 的表达。通过流式细胞术分析分离的核悬浮液以确定 NF-kappaB 的激活。

结果

CAO 和 T+CAO 组的危险区（左心室百分比）分别为 46.4±6.2%和 48.2±5.9%，两组之间的危险区/左心室面积无统计学差异（P＞0.05）。CAO 组的梗死面积（危险区百分比）从 44.9±6.8%减少到 T+CAO 组的 31.6±7.7%。T+CAO 组的梗死面积减少具有统计学意义（P＜0.05）。与假手术组相比，CAO 组 NF-kappaB 及其 mRNA 和细胞间黏附分子-1mRNA 的表达显著增加，而 T+CAO 动物中的表达显著降低。流式细胞术检测显示曲马多可使 NF-kappaB 的激活减少 13.4%。