Tähepõld Peeter, Vaage Jarle, Starkopf Joel, Valen Guro
Crafoord Laboratory of Experimental Surgery, Karolinska Hospital, Stockholm, Sweden.
J Thorac Cardiovasc Surg. 2003 Mar;125(3):650-60. doi: 10.1067/mtc.2003.36.
Hyperoxia has been previously shown to protect the heart from ischemia-reperfusion injury. In the present study we investigated whether the cardioprotective effects of hyperoxia were dependent on the redox-sensitive transcription factor nuclear factor kappaB.
Rats were kept in a hyperoxic (> or =95% O(2)) environment for 60 minutes. Their hearts were isolated immediately afterward, buffer perfused in a Langendorff apparatus, and subjected to 25 minutes of global ischemia and 60 minutes of reperfusion. Cardiac pressures and coronary flow were measured, and infarct size was determined by means of triphenyl tetrazolium chloride staining. Activation of nuclear factor kappaB was assessed by means of the electrophoretic mobility shift assay, whereas the inhibitor IkappaBalpha was evaluated by means of immunoblotting. Pharmacologic inhibition of nuclear factor kappaB was achieved with 2 different agents, SN50 and pyrrolidine dithiocarbamate.
Preischemic exposure to hyperoxia improved postischemic recovery of myocardial contractile function and coronary flow and reduced infarct size. Hyperoxia activated pulmonary and myocardial nuclear factor kappaB. Pretreatment with SN50 (400 microg/kg administered intraperitoneally) or pyrrolidine dithiocarbamate (100 mg/kg administered intraperitoneally) before hyperoxia abolished the functional and infarct-limiting protection. Hyperoxia reduced nuclear factor kappaB activation in the heart during sustained ischemia and reperfusion and increased the cytoplasmatic inhibitory factor IkappaBalpha. Administration of pyrrolidine dithiocarbamate or SN50 during ischemia and reperfusion to isolated hearts from normoxic control animals improved postischemic contractile function and coronary flow and reduced infarct size.
Hyperoxia protects the rat heart against ischemia-reperfusion injury. The cardioprotection depends on myocardial activation of the transcription factor nuclear factor kappaB. Our results support evidence for a dual role of nuclear factor kappaB in the heart.
先前的研究表明，高氧可保护心脏免受缺血-再灌注损伤。在本研究中，我们调查了高氧的心脏保护作用是否依赖于对氧化还原敏感的转录因子核因子κB。
将大鼠置于高氧（≥95% O₂）环境中60分钟。随后立即取出心脏，在Langendorff装置中用缓冲液灌注，并进行25分钟的全心缺血和60分钟的再灌注。测量心脏压力和冠状动脉血流，并用氯化三苯基四氮唑染色法测定梗死面积。通过电泳迁移率变动分析评估核因子κB的激活，而通过免疫印迹法评估抑制剂IκBα。用两种不同的药物SN50和吡咯烷二硫代氨基甲酸盐对核因子κB进行药理学抑制。
缺血前暴露于高氧可改善缺血后心肌收缩功能和冠状动脉血流的恢复，并减小梗死面积。高氧激活了肺和心肌中的核因子κB。在高氧之前用SN50（腹腔注射400μg/kg）或吡咯烷二硫代氨基甲酸盐（腹腔注射100mg/kg）预处理可消除功能和梗死限制保护作用。高氧在持续缺血和再灌注期间降低了心脏中核因子κB的激活，并增加了细胞质抑制因子IκBα。在缺血和再灌注期间向来自常氧对照动物的离体心脏施用吡咯烷二硫代氨基甲酸盐或SN50可改善缺血后收缩功能和冠状动脉血流，并减小梗死面积。
高氧可保护大鼠心脏免受缺血-再灌注损伤。心脏保护作用取决于转录因子核因子κB的心肌激活。我们的结果支持核因子κB在心脏中具有双重作用的证据。
