Brown David A, Lynch Joshua M, Armstrong Casey J, Caruso Nicholas M, Ehlers Lindsay B, Johnson Micah S, Moore Russell L
Department of Integrative Physiology, University of Colorado Cardiovascular Institute, University of Colorado at Boulder, Boulder, CO 80309-0354, USA.
J Physiol. 2005 Apr 15;564(Pt 2):619-30. doi: 10.1113/jphysiol.2004.081323. Epub 2005 Feb 17.
The cardioprotective effects of short-term exercise against myocardial ischaemia-reperfusion injury in male and female rats were examined. We subjected male and female rats to 0 (Sed; n = 8 males and 8 females), 1 (1 day; n = 10 males and 8 females), or 5 (5 day; n = 6 males and 6 females) days of treadmill running. Langendorff-perfused hearts underwent 1 h of regional ischaemia and 2 h of reperfusion, and infarct size (expressed as a percentage of the zone at risk; ZAR), left ventricular pressure development, and coronary flow were measured for each heart. Preischaemic pressure development and coronary flow did not differ between the sexes nor were they influenced by exercise. Sed females had significantly smaller infarct sizes (25 +/- 3%) than Sed male hearts (37 +/- 3%; P < 0.001). Short-term running significantly reduced infarct size following 1 day (27 +/- 3%; P < 0.05) and 5 days (30 +/- 4%; P < 0.10) of exercise in males. One day of running did not reduce infarct size in females (19 +/- 3%; P = NS), but 5 day females did show a significant reduction in infarct size (13 +/- 2%; P < 0.05). There was no relationship between postischaemic coronary vascular hyperaemia and infarct size across sexes or exercise training groups. Hearts from Sed females exhibited significantly higher manganese superoxide dismutase (MnSOD) protein expression than hearts from Sed males, but short-term exercise (neither 1 nor 5 days) did not alter MnSOD protein in either sex. Increased sarcolemmal ATP-sensitive K(+) (K(ATP)) channel subunit protein expression (SUR2A and/or K(ir)6.2) correlated closely with sex-dependent and exercise-acquired protection against myocardial infarction. These data indicate that: (1) sex-dependent and exercise-induced differences in the susceptibility of the heart to ischaemia-reperfusion injury are not associated with improved coronary flow or postischaemic hyperaemia; (2) increased MnSOD protein expression is not necessary for exercise-induced protection from infarction; and (3) one possible mechanism for sex-dependent and exercise-mediated reductions in infarct size involves an increased protein expression of cardiac sarcolemmal K(ATP) channels.
研究了短期运动对雄性和雌性大鼠心肌缺血再灌注损伤的心脏保护作用。我们将雄性和雌性大鼠分别进行0天（静息组；8只雄性和8只雌性）、1天（1天运动组；10只雄性和8只雌性）或5天（5天运动组；6只雄性和6只雌性）的跑步机跑步训练。采用Langendorff灌流心脏，使其经历1小时的局部缺血和2小时的再灌注，然后测量每颗心脏的梗死面积（以危险区域的百分比表示；ZAR）、左心室压力变化以及冠状动脉血流量。缺血前的压力变化和冠状动脉血流量在性别之间没有差异，也不受运动的影响。静息组雌性大鼠的梗死面积（25±3%）显著小于静息组雄性大鼠（37±3%；P<0.001）。在雄性大鼠中，短期跑步在运动1天（27±3%；P<0.05）和5天（30±4%；P<0.10）后显著减小了梗死面积。运动1天对雌性大鼠的梗死面积没有减小作用（19±3%；P=无显著性差异），但运动5天的雌性大鼠梗死面积显著减小（13±2%；P<0.05）。缺血后冠状动脉血管充血与性别或运动训练组的梗死面积之间没有关系。静息组雌性大鼠心脏的锰超氧化物歧化酶（MnSOD）蛋白表达显著高于静息组雄性大鼠，但短期运动（1天和5天）均未改变两性的MnSOD蛋白表达。肌膜ATP敏感性钾（K(ATP)）通道亚基蛋白表达（SUR2A和/或K(ir)6.2）的增加与性别依赖性及运动获得性的心肌梗死保护密切相关。这些数据表明：（1）心脏对缺血再灌注损伤易感性的性别依赖性和运动诱导差异与冠状动脉血流量改善或缺血后充血无关；（2）运动诱导的梗死保护作用并不需要增加MnSOD蛋白表达；（3）性别依赖性和运动介导的梗死面积减小的一种可能机制涉及心脏肌膜K(ATP)通道蛋白表达增加。
