缺血预处理减轻心肌缺血再灌注诱导的Na^+-K^+-ATP酶异常表达

Ischemic preconditioning attenuates ischemia-reperfusion-induced abnormality of Na^+-K^+-ATPase protein expression in hearts

目的:探讨Na+-K+-ATP酶在心肌缺血预处理保护机制中的作用。方法:以前降支结扎30 min后复灌60 min制备心肌缺血再灌注模型,连续3次缺血5 min再灌注10 min制备缺血预处理模型。以毛花甙丙抑制Na+-K+-ATP酶功能,观察心脏收缩和舒张功能、心肌Na+-K+-ATP酶功能,免疫组化法检测Na+-K+-ATP酶α1、2α、α3及1β亚基的蛋白表达。结果:心肌缺血再灌注显著抑制心脏舒缩功能、Na+-K+-ATP酶活性以及1α、2α、3α及β1亚基的蛋白原位表达;缺血预处理可减轻心肌缺血再灌注诱导的Na+-K+-ATP酶异常,保护心脏功能;毛花甙丙可维持心脏舒缩功能,但显著抑制Na+-K+-ATP酶和蛋白表达。结论:缺血预处理能减轻心肌缺血再灌注诱导的Na+-K+-ATP酶异常,抑制Na+-K+-ATP酶功能导致缺血预处理保护作用丧失,维持Na+-K+-ATP酶功能是缺血预处理心肌保护重要机制之一。

AIM： To study the role of Na^＋ -K^＋ -ATPase in the protective mechanism of ischemic preconditioning （IP） on myocardial ischemia and reperfusion injury. METHODS： Ligation of anterior descending branch of rat hearts for 30 min （ischemia） and reperfusion for 60 min were for establishing the model of ischemia/reperfusion （I/R）, and 5 min of ischemia and 10 min of reperfusion were made for three cycles with a view to preparing IP model. After hemodynamic data were recorded, myocardium sample was processed immediately in order to measure the activity of Na^＋ -K^＋ -ATPase and Ca^2＋ -Mg^2 ＋ - ATPase and the changes of protein expression of αl, α2, α3 and β1 isoforms of Na^＋ -K^＋ -ATPase. RESULTS： I/R reduced cardiac contractile and diastolic function, activity of Na^＋ -K^＋ -ATPase and Ca^2 ＋ -Mg^2 ＋ -ATPase, and protein expression of αl, α2, α3 and βl isoforms of Na^＋ -K^＋ -ATPase. IP attenuated the reduction of cardiac function, the activities and protein expression of Na^＋ -K^＋ -ATPase αl, α2, α3 and β1-isoforms induced by I/R. Digilanid C abolished the effects of IP on Na^＋ -K^＋ -ATPase. CONCLUSION： The beneficial effects of IP on the prohibition of Na^＋ -K^＋ -ATPase induced by myocardial ischemia and reperfusion were abolished by cardiac glycoside. Protecting Na^＋ -K^＋ -ATPase may play an important role in the mechanism of IP. KEY WORDS