Rathi Satyajeet S, Xu Yan-Jun, Dhalla Naranjan S
Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba.
Exp Clin Cardiol. 2002 Fall;7(2-3):146-50.
Tumour necrosis factor alphs (TNF-alpha), a proinflammatory cytokine, is synthesized in the heart under pathologic conditions; however, it is not clear whether this cytokine results in heart dysfunction or serves as a cardioprotective agent.
To examine whether TNF-alpha in low concentrations exerts a cardioprotective effect on the heart and prevents the occurrence of intracellular calcium overload.
The effect of TNF-alpha was studied in vivo on hemodynamic parameters in anesthetized rats. The cardioprotective action of TNF-alpha was tested against ischemia-reperfusion-induced changes in cardiac performance in the isolated perfused rat hearts. The effect of TNF-alpha on intracellular free calcium was evaluated in freshly isolated adult rat cardiomyocytes by Fura 2 technique.
An intravenous injection of TNF-alpha (200 mug/kg) in rats produced a transient but significant depressant effect on cardiac function and an increase in heart rate. TNF-alpha (25 mug/mL) did not affect cardiac function in the isolated heart; however, it attenuated the ischemia-reperfusion-induced changes in the left ventricular pressures (developed pressure, end diastolic pressure, +dP/dt and -dP/dt). In the isolated cardiomyocytes, TNF-alpha did not produce any change in the level of intracellular free calcium, but this agent (10 to 100 ng/mL) significantly decreased the potassium chloride (30 mM) -induced increase in free calcium.
The inhibitory effect of low concentrations of TNF-alpha on calcium influx may reduce the occurrence of intracellular calcium overload, and this may be responsible for improving left ventricular dysfunction due to ischemia-reperfusion injury in the heart.
肿瘤坏死因子α（TNF-α）是一种促炎细胞因子，在病理条件下可在心脏中合成；然而，尚不清楚这种细胞因子是导致心脏功能障碍还是作为一种心脏保护剂。
研究低浓度的TNF-α是否对心脏具有心脏保护作用，并预防细胞内钙超载的发生。
在体内研究TNF-α对麻醉大鼠血流动力学参数的影响。测试TNF-α对离体灌注大鼠心脏缺血再灌注诱导的心脏功能变化的心脏保护作用。采用Fura 2技术在新鲜分离的成年大鼠心肌细胞中评估TNF-α对细胞内游离钙的影响。
给大鼠静脉注射TNF-α（200μg/kg）对心脏功能产生短暂但显著的抑制作用，并使心率增加。TNF-α（25μg/mL）对离体心脏的心脏功能无影响；然而，它减轻了缺血再灌注诱导的左心室压力变化（收缩压、舒张末期压力、+dP/dt和-dP/dt）。在分离的心肌细胞中，TNF-α对细胞内游离钙水平没有产生任何变化，但该药物（10至100 ng/mL）显著降低了氯化钾（30 mM）诱导的游离钙增加。
低浓度的TNF-α对钙内流的抑制作用可能减少细胞内钙超载的发生，这可能是改善心脏缺血再灌注损伤所致左心室功能障碍的原因。
